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The Effect of Radiotherapy on Local Regional Recurrence among Patients with Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer
I. J. Radiation Oncology d Biology d Physics
S96
205
Volume 78, Number 3, Supplement, 2010
Locoregional Recurrence Risks in Women with Nodal Micrometastatic Breast Cancer
K. K. Lupe1, P. T. Truong1, C. Alexander1, C. Speers2, S. Tyldesley3 1
British Columbia Cancer Agency, Vancouver Island Centre, Victoria, BC, Canada, 2Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC, Canada, 3British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC, Canada Purpose/Objective(s): The implication of breast cancer with nodal micrometastases measuring .0.2mm but #2mm (pNmic) on locoregional recurrence (LRR) risk is unclear. This study evaluates: 1. locoregional recurrence (LRR) outcomes in women with nodal micrometastases (pNmic), compared to node-negative (pN0) and macroscopic node-positive (pNmac) breast cancer; 2. LRR according to locoregional treatment of pNmic disease. Materials/Methods: The study cohort comprised 9616 women referred between 1989-99 with pT1-2, pN0, pNmic and pNmac, M0 breast cancer. All women underwent axillary dissection. Ten-year Kaplan-Meier (KM) local (LR), regional (RR) and locoregional (LRR) recurrence rates were compared between patients with pN0 (n = 7977), pNmic (n = 490) and pNmac (n = 1149) disease. Treatment practices within pNmic patients were evaluated and the ten-year KM LRR rates were compared between treatment groups. Cox regression analyses were performed to identify significant factors associated with LRR. Results: The median follow-up time was 11 yrs. The median number of nodes removed was 10 (1-52). Fifty-two percent of women received systemic therapy. Ten-year KM outcomes in the pN0, pNmic and pNmac cohorts were: LR (6.1%, 6.8%, 8.7%, p \ 0.001), RR (3.1%, 6.2%, 10.3%, p \ 0.001), and LRR (8.0%, 11.6%, 15.2%, p \ 0.001). Among pNmic patients, 248 (50.6%) had breast conserving surgery (BCS) and 242 (49.4%) had mastectomy (Mx). Nodal RT was used in 121 (24.7%) pNmic patients. In pNmic patients treated with BCS, 10-yr RR rates were 6.4% with BCS + breast only RT (n = 178), and 5.4% with BCS + breast and nodal RT (n = 62). In pNmic patients treated with Mx, 10-year RR rates were 4.6% with Mx alone (n = 173), 11.1% with Mx + chest wall RT (n = 10) and 10.7% with Mx + chest wall and nodal RT (n = 59). In women with pNmic disease, age \45 years, grade 3 histology, lymphovascular invasion (LVI), nodal ratio $0.25, absence of systemic therapy and estrogen receptor-negative disease were factors associated with 10-year KM LRR risks of 15-20%. On multivariate analysis of the entire cohort, pNmic was associated with higher LRR compared to pN0 (HR 1.6, p = 0.002). On multivariate analysis of pNmic patients only, age \45 years was significantly associated with higher RR (HR 3.1, p = 0.005) and LRR (HR 1.9, p = 0.03), while trends for higher LRR were observed with nodal ratio $0.25 (HR 2.0, p = 0.07) and LVI (HR 1.7, p = 0.07). Conclusions: Women with nodal micrometastatic breast cancer experienced higher rates of LRR compared to pN0 disease. Young age was associated with high LRR warranting consideration of locoregional radiotherapy. Author Disclosure: K.K. Lupe, None; P.T. Truong, None; C. Alexander, None; C. Speers, None; S. Tyldesley, None.
206
The Effect of Radiotherapy on Local Regional Recurrence among Patients with Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer
C. E. Fasola1, K. D. Godette2, M. W. McDonald3, R. M. O’Regan4, A. B. Zelnak5, J. C. Landry6, M. A. Torres6 1 Emory University School of Medicine, Atlanta, GA, 2Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 3Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, 4 Department of Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 5Department of Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 6Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA
Purpose/Objective(s): Neoadjuvant chemotherapy is increasingly used in the management of locally advanced breast cancer and in select Stage I, II tumors. Post-mastectomy radiation therapy (PMRT) has been shown to reduce local regional recurrence rates (LRR); however, indications for PMRT following pathologic complete response (pCR) to neoadjuvant chemotherapy remain unclear. The aim of this study was to evaluate the rates of LRR among pCR patients treated with breast conserving therapy (BCT) or mastectomy with or without radiation (XRT). Materials/Methods: The case histories of 378 patients with breast cancer treated with neoadjuvant chemotherapy and surgery with or without XRT from March 1997 to January 2010 were analyzed. Median age at diagnosis was 49 years (range: 22-84). The clinical stage at diagnosis was I in 4 (1%), IIA in 122 (36%), IIB in 103 (30%), IIIA in 87 (25%), IIIB in 25 (7%) and IIIC in 4 (1%) patients. All patients received neoadjuvant chemotherapy consisting of doxorubicin-based (92%) or taxane-based (8%) regimens. Patients then underwent either breast conserving surgery followed by XRT (n = 168, 45%) or modified radical mastectomy (n = 207, 55%) with (n = 144, 70%) or without PMRT (n = 63, 30%). Median follow-up time was 41 months. All analyses were performed using SAS software, version 9.2 (SAS Institute, Cary, NC). Results: Of 378 patients, 72 (19%) achieved a pCR to neoadjuvant chemotherapy, 40 (56%) of whom were treated with BCT and 32 (44%) with mastectomy (n = 22 in PMRT group, n = 10 in non-PMRT group). BCT patients who achieved pCR compared to those who did not had similar rates of local control (97% vs. 93%, p = 0.8), disease-free survival (DFS; 86% vs. 81%, p = 0.5) and overall survival (OS; 90% vs. 95%, p = 0.8) at 3 years. Among all mastectomy patients, XRT improved local control (95% vs. 83%, p = 0.06) with the most common site of recurrence being chest wall (n = 5, 56%) followed by axilla (n = 2, 22%) and supraclavicular fossa (n = 2, 22%). The clinical stage of mastectomy patients who did not receive XRT and experienced a LRR was IIA in 2 (22%), IIB in 5 (56%), IIIA in 1(11%) and IIIB in 1(11%). Among pCR post mastectomy patients, XRT appeared to improve local control (100% vs. 89%, p = 0.3) and distant metastasis free survival (100% vs. 78%, p = 0.08) at 3 years. Mastectomy patients who achieved pCR did significantly better than those who did not (3 year DFS 91% vs. 65%, p = 0.007; and OS 100% vs. 72%, p = 0.003). Conclusions: Mastectomy patients who achieve a pCR to neoadjuvant chemotherapy have high rates of local regional recurrence and may benefit from radiation therapy. Further studies regarding the role of radiation therapy in mastectomy patients following neoadjuvant chemotherapy are needed. Author Disclosure: C.E. Fasola, None; K.D. Godette, None; M.W. McDonald, None; R.M. O’Regan, None; A.B. Zelnak, None; J.C. Landry, None; M.A. Torres, None.
S96
205
Volume 78, Number 3, Supplement, 2010
Locoregional Recurrence Risks in Women with Nodal Micrometastatic Breast Cancer
K. K. Lupe1, P. T. Truong1, C. Alexander1, C. Speers2, S. Tyldesley3 1
British Columbia Cancer Agency, Vancouver Island Centre, Victoria, BC, Canada, 2Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC, Canada, 3British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC, Canada Purpose/Objective(s): The implication of breast cancer with nodal micrometastases measuring .0.2mm but #2mm (pNmic) on locoregional recurrence (LRR) risk is unclear. This study evaluates: 1. locoregional recurrence (LRR) outcomes in women with nodal micrometastases (pNmic), compared to node-negative (pN0) and macroscopic node-positive (pNmac) breast cancer; 2. LRR according to locoregional treatment of pNmic disease. Materials/Methods: The study cohort comprised 9616 women referred between 1989-99 with pT1-2, pN0, pNmic and pNmac, M0 breast cancer. All women underwent axillary dissection. Ten-year Kaplan-Meier (KM) local (LR), regional (RR) and locoregional (LRR) recurrence rates were compared between patients with pN0 (n = 7977), pNmic (n = 490) and pNmac (n = 1149) disease. Treatment practices within pNmic patients were evaluated and the ten-year KM LRR rates were compared between treatment groups. Cox regression analyses were performed to identify significant factors associated with LRR. Results: The median follow-up time was 11 yrs. The median number of nodes removed was 10 (1-52). Fifty-two percent of women received systemic therapy. Ten-year KM outcomes in the pN0, pNmic and pNmac cohorts were: LR (6.1%, 6.8%, 8.7%, p \ 0.001), RR (3.1%, 6.2%, 10.3%, p \ 0.001), and LRR (8.0%, 11.6%, 15.2%, p \ 0.001). Among pNmic patients, 248 (50.6%) had breast conserving surgery (BCS) and 242 (49.4%) had mastectomy (Mx). Nodal RT was used in 121 (24.7%) pNmic patients. In pNmic patients treated with BCS, 10-yr RR rates were 6.4% with BCS + breast only RT (n = 178), and 5.4% with BCS + breast and nodal RT (n = 62). In pNmic patients treated with Mx, 10-year RR rates were 4.6% with Mx alone (n = 173), 11.1% with Mx + chest wall RT (n = 10) and 10.7% with Mx + chest wall and nodal RT (n = 59). In women with pNmic disease, age \45 years, grade 3 histology, lymphovascular invasion (LVI), nodal ratio $0.25, absence of systemic therapy and estrogen receptor-negative disease were factors associated with 10-year KM LRR risks of 15-20%. On multivariate analysis of the entire cohort, pNmic was associated with higher LRR compared to pN0 (HR 1.6, p = 0.002). On multivariate analysis of pNmic patients only, age \45 years was significantly associated with higher RR (HR 3.1, p = 0.005) and LRR (HR 1.9, p = 0.03), while trends for higher LRR were observed with nodal ratio $0.25 (HR 2.0, p = 0.07) and LVI (HR 1.7, p = 0.07). Conclusions: Women with nodal micrometastatic breast cancer experienced higher rates of LRR compared to pN0 disease. Young age was associated with high LRR warranting consideration of locoregional radiotherapy. Author Disclosure: K.K. Lupe, None; P.T. Truong, None; C. Alexander, None; C. Speers, None; S. Tyldesley, None.
206
The Effect of Radiotherapy on Local Regional Recurrence among Patients with Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer
C. E. Fasola1, K. D. Godette2, M. W. McDonald3, R. M. O’Regan4, A. B. Zelnak5, J. C. Landry6, M. A. Torres6 1 Emory University School of Medicine, Atlanta, GA, 2Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 3Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, 4 Department of Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 5Department of Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 6Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA
Purpose/Objective(s): Neoadjuvant chemotherapy is increasingly used in the management of locally advanced breast cancer and in select Stage I, II tumors. Post-mastectomy radiation therapy (PMRT) has been shown to reduce local regional recurrence rates (LRR); however, indications for PMRT following pathologic complete response (pCR) to neoadjuvant chemotherapy remain unclear. The aim of this study was to evaluate the rates of LRR among pCR patients treated with breast conserving therapy (BCT) or mastectomy with or without radiation (XRT). Materials/Methods: The case histories of 378 patients with breast cancer treated with neoadjuvant chemotherapy and surgery with or without XRT from March 1997 to January 2010 were analyzed. Median age at diagnosis was 49 years (range: 22-84). The clinical stage at diagnosis was I in 4 (1%), IIA in 122 (36%), IIB in 103 (30%), IIIA in 87 (25%), IIIB in 25 (7%) and IIIC in 4 (1%) patients. All patients received neoadjuvant chemotherapy consisting of doxorubicin-based (92%) or taxane-based (8%) regimens. Patients then underwent either breast conserving surgery followed by XRT (n = 168, 45%) or modified radical mastectomy (n = 207, 55%) with (n = 144, 70%) or without PMRT (n = 63, 30%). Median follow-up time was 41 months. All analyses were performed using SAS software, version 9.2 (SAS Institute, Cary, NC). Results: Of 378 patients, 72 (19%) achieved a pCR to neoadjuvant chemotherapy, 40 (56%) of whom were treated with BCT and 32 (44%) with mastectomy (n = 22 in PMRT group, n = 10 in non-PMRT group). BCT patients who achieved pCR compared to those who did not had similar rates of local control (97% vs. 93%, p = 0.8), disease-free survival (DFS; 86% vs. 81%, p = 0.5) and overall survival (OS; 90% vs. 95%, p = 0.8) at 3 years. Among all mastectomy patients, XRT improved local control (95% vs. 83%, p = 0.06) with the most common site of recurrence being chest wall (n = 5, 56%) followed by axilla (n = 2, 22%) and supraclavicular fossa (n = 2, 22%). The clinical stage of mastectomy patients who did not receive XRT and experienced a LRR was IIA in 2 (22%), IIB in 5 (56%), IIIA in 1(11%) and IIIB in 1(11%). Among pCR post mastectomy patients, XRT appeared to improve local control (100% vs. 89%, p = 0.3) and distant metastasis free survival (100% vs. 78%, p = 0.08) at 3 years. Mastectomy patients who achieved pCR did significantly better than those who did not (3 year DFS 91% vs. 65%, p = 0.007; and OS 100% vs. 72%, p = 0.003). Conclusions: Mastectomy patients who achieve a pCR to neoadjuvant chemotherapy have high rates of local regional recurrence and may benefit from radiation therapy. Further studies regarding the role of radiation therapy in mastectomy patients following neoadjuvant chemotherapy are needed. Author Disclosure: C.E. Fasola, None; K.D. Godette, None; M.W. McDonald, None; R.M. O’Regan, None; A.B. Zelnak, None; J.C. Landry, None; M.A. Torres, None.