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IN12 INOPERABLE LOCALLY ADVANCED BREAST CANCER: SURGERY – CHALLENGES AND OPPORTUNITIES
S22
Abstracts / The Breast 22 S3 (2013) S19–S63
randomized trial [2] showed that loco-regional radiotherapy following mastectomy and adjuvant chemotherapy improves not only loco-regional control, but overall survival as well. A subsequent analysis of the Danish trials [3] showed that the largest gain in local control was found in patients with the most advanced tumors (T3, > 3 nodes positive, grade 3), while the survival benefit was mainly found in the lower risk patients. Even though it has been demonstrated that tri-modality therapy (surgery, systemic treatment and radiotherapy) accomplishes the best local control, some questions about the timing of these treatments are still unanswered. Usually treatment starts with surgery or, in the case of primary inoperable disease, with chemotherapy. Some studies have evaluated the role of preoperative radiotherapy, either sequentially or concomitantly with chemotherapy. The results in terms of response rates are very encouraging; however, toxicity can be important with the concomitant schedules. After neo-adjuvant chemotherapy followed by mastectomy, the indication for postoperative radiotherapy should be based on the initial tumor stage. Even following a pathological complete response to neo-adjuvant chemotherapy, local recurrence rates can be high in the absence of postoperative radiotherapy. An unresolved problem is the combination of postoperative radiotherapy and breast reconstruction after mastectomy. Radiotherapy negatively influences the cosmetic result of a reconstruction. Immediate reconstruction with a prosthesis followed by radiotherapy leads to significant capsular contraction in 30 to 40% of patients. An alternative solution would be to perform a reconstruction with a tissue flap after radiotherapy. For LABC patients that cannot be treated with immediate surgery or surgery following neo-adjuvant chemotherapy, radiotherapy can be combined with hyperthermia to enhance the tumoricidal effect of the radiotherapy. This combination is also very effective for patients presenting chest wall recurrences after an initial treatment including radiotherapy. The Danish and Canadian studies used radiotherapy to the chest wall combined with irradiation of the nodal areas. Since most recurrences after mastectomy are located on the chest wall, this area should be treated in all patients where postoperative radiotherapy is indicated. After axillary dissection, the local recurrence rate in the operated area is very low. However, with four or more positive lymph nodes, the probability of a periclavicular recurrence is 10 to 20%, necessitating irradiation of the nodal areas not treated by surgery (level III and the supraclavicular area). The results of the EORTC trial [4] investigating the need for internal mammary nodes (IMN) irradiation are not known yet. However, a French study [5] did not show any survival benefit related to IMN irradiation. Since including the IMN in the radiotherapy field significantly increases the irradiated lung volume and (for left sided breast cancer patients) the heart volume, the only real indication for IMN radiotherapy is proven IMN nodal metastases or strong suspicion, with, for example, PET positivity. [1] Nielsen HM, Overgaard M, Grau C, et al. Study of failure pattern among high-risk breast cancer patients with or without postmastectomy radiotherapy in addition to adjuvant systemic therapy: long-term results from the Danish Breast Cancer Cooperative Group DBCG 82 b and c randomized studies. J Clin Oncol 2006; 24:2268-75 [2] Ragaz J, Olivotto IA, Spinelli JJ, et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst. 2005; 97:116-26 [3] Kyndi M, Overgaard M, Nielsen HM, et al. High local recurrence risk is not associated with large survival reduction after postmastectomy radiotherapy in high-risk breast cancer: a subgroup analysis of DBCG 82 b&c. Radiother Oncol. 2009; 90:74-9 [4] Matzinger O, Heimsoth I, Poortmans P, et al. Toxicity at three years with and without irradiation of the internal mammary and medial supraclavicular lymph node chain in stage I to III breast cancer (EORTC trial 22922/10925). Acta Oncol.2010;4 9:24-34 [5] Hennequin C, Bossard N, Servagi-Vernat S, et al. Ten-year survival results of a randomized trial of irradiation of internal mammary nodes after mastectomy. Int J Radiat Oncol Biol Phys. 2013; 86:860-6
IN12 INOPERABLE LOCALLY ADVANCED BREAST CANCER: SURGERY - CHALLENGES AND OPPORTUNITIES M.J. Cardoso Breast Unit, Champalimaud Foundation, Lisbon, Portugal Locally advanced breast cancer (LABC) occurs at presentation in one fifth of breast cancer patients worldwide but with much lesser incidence in countries with established screening programs. LABC includes large operable primary breast tumors (stage IIB, IIIA) and/or those involving the skin or chest wall and/or those with extensive lymphadenopathy (stage IIIB, IIIC). A distinct form of LABC is inflammatory breast cancer (IBC). In summary LABC is a very heterogeneous entity with different biology cancers carrying however a common factor – a worse prognosis. For a long time mastectomy was the mainstay of treatment in those patients, however local recurrences were high (50%) and survival very low (2-5% OS). The addition of radiotherapy after surgery decreased loco-regional recurrences but survival remained very low. Adding systemic therapy to surgery and radiotherapy objectively improved outcomes. Currently a combination of systemic treatments with surgery and radiation is the standard of care in LABC due to improvement of loco-regional control and survival. Regarding loco-regional approach there are three main groups in LABC: large operable, inoperable and inflammatory tumors. Surgery after induction systemic therapy in LABC allows breast conservative surgery in variable percentages depending on tumor/ patient characteristics. Mastectomy remains the option before or after radiotherapy for those patients not amenable to conservation treatment and for all patients with IBC. Whenever mastectomy is possible patients should have the option to undergo either immediate (IBR) or delayed breast reconstruction. When IBR is considered major concerns are the risk of increased complications, compromised cosmesis and difficulties in planning radiotherapy even if there are no data from randomized trials confirming these potential issues. However, a minority of those patients remain inoperable, even after systemic therapy and radiotherapy, and represent one of the most difficult challenges to multidisciplinary teams. Salvage and debulking surgery have been described in a limited number of cases where local control remains the major concern. In this particular setting thoracic wall reconstruction, if feasible, is a necessity in the majority of interventions. Regarding axillary status and even after a complete clinical/imaging response with neo-adjuvant systemic therapy, clearance is the current recommendation after a positive pre-treatment staging and in IBC cancer. Treatment of LABC is a therapeutic challenge, encompassing a heterogeneous group of lesions, and treatment decisions must be undertaken understanding that in view of minor evidence from randomized studies most of the patients will be managed empirically supported by what should be a dedicated multidisciplinary expert approach. [1] Giordano SH. Update on locally advanced breast cancer. Oncologist. 2003;8(6):521-30 [2] Gonzalez-Angulo AM, Hennessy BT, Broglio K, Meric-Bernstam F, Cristofanilli M, Giordano SH, Buchholz TA, Sahin A, Singletary SE, Buzdar AU, Hortobágyi GN. Trends for inflammatory breast cancer: is survival improving? Oncologist. 2007 Aug;12(8):904-12 [3] Chia S, Swain SM, Byrd DR, Mankoff DA. Locally advanced and inflammatory breast cancer. J Clin Oncol. 2008 Feb 10;26(5):786-90 [4] Dawood S, Merajver SD, Viens P, Vermeulen PB, Swain SM, Buchholz TA, Dirix LY, Levine PH, Lucci A, Krishnamurthy S, Robertson FM, Woodward WA, Yang WT, Ueno NT, Cristofanilli M. International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Ann Oncol. 2011 Mar;22(3):515-23 [5] Cox C, Holloway CM, Shaheta A, Nofech-Mozes S, Wright FC. What is the burden of axillary disease after neoadjuvant therapy in women with locally advanced breast cancer? Curr Oncol. 2013 Apr;20(2):111-7
Abstracts / The Breast 22 S3 (2013) S19–S63
randomized trial [2] showed that loco-regional radiotherapy following mastectomy and adjuvant chemotherapy improves not only loco-regional control, but overall survival as well. A subsequent analysis of the Danish trials [3] showed that the largest gain in local control was found in patients with the most advanced tumors (T3, > 3 nodes positive, grade 3), while the survival benefit was mainly found in the lower risk patients. Even though it has been demonstrated that tri-modality therapy (surgery, systemic treatment and radiotherapy) accomplishes the best local control, some questions about the timing of these treatments are still unanswered. Usually treatment starts with surgery or, in the case of primary inoperable disease, with chemotherapy. Some studies have evaluated the role of preoperative radiotherapy, either sequentially or concomitantly with chemotherapy. The results in terms of response rates are very encouraging; however, toxicity can be important with the concomitant schedules. After neo-adjuvant chemotherapy followed by mastectomy, the indication for postoperative radiotherapy should be based on the initial tumor stage. Even following a pathological complete response to neo-adjuvant chemotherapy, local recurrence rates can be high in the absence of postoperative radiotherapy. An unresolved problem is the combination of postoperative radiotherapy and breast reconstruction after mastectomy. Radiotherapy negatively influences the cosmetic result of a reconstruction. Immediate reconstruction with a prosthesis followed by radiotherapy leads to significant capsular contraction in 30 to 40% of patients. An alternative solution would be to perform a reconstruction with a tissue flap after radiotherapy. For LABC patients that cannot be treated with immediate surgery or surgery following neo-adjuvant chemotherapy, radiotherapy can be combined with hyperthermia to enhance the tumoricidal effect of the radiotherapy. This combination is also very effective for patients presenting chest wall recurrences after an initial treatment including radiotherapy. The Danish and Canadian studies used radiotherapy to the chest wall combined with irradiation of the nodal areas. Since most recurrences after mastectomy are located on the chest wall, this area should be treated in all patients where postoperative radiotherapy is indicated. After axillary dissection, the local recurrence rate in the operated area is very low. However, with four or more positive lymph nodes, the probability of a periclavicular recurrence is 10 to 20%, necessitating irradiation of the nodal areas not treated by surgery (level III and the supraclavicular area). The results of the EORTC trial [4] investigating the need for internal mammary nodes (IMN) irradiation are not known yet. However, a French study [5] did not show any survival benefit related to IMN irradiation. Since including the IMN in the radiotherapy field significantly increases the irradiated lung volume and (for left sided breast cancer patients) the heart volume, the only real indication for IMN radiotherapy is proven IMN nodal metastases or strong suspicion, with, for example, PET positivity. [1] Nielsen HM, Overgaard M, Grau C, et al. Study of failure pattern among high-risk breast cancer patients with or without postmastectomy radiotherapy in addition to adjuvant systemic therapy: long-term results from the Danish Breast Cancer Cooperative Group DBCG 82 b and c randomized studies. J Clin Oncol 2006; 24:2268-75 [2] Ragaz J, Olivotto IA, Spinelli JJ, et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst. 2005; 97:116-26 [3] Kyndi M, Overgaard M, Nielsen HM, et al. High local recurrence risk is not associated with large survival reduction after postmastectomy radiotherapy in high-risk breast cancer: a subgroup analysis of DBCG 82 b&c. Radiother Oncol. 2009; 90:74-9 [4] Matzinger O, Heimsoth I, Poortmans P, et al. Toxicity at three years with and without irradiation of the internal mammary and medial supraclavicular lymph node chain in stage I to III breast cancer (EORTC trial 22922/10925). Acta Oncol.2010;4 9:24-34 [5] Hennequin C, Bossard N, Servagi-Vernat S, et al. Ten-year survival results of a randomized trial of irradiation of internal mammary nodes after mastectomy. Int J Radiat Oncol Biol Phys. 2013; 86:860-6
IN12 INOPERABLE LOCALLY ADVANCED BREAST CANCER: SURGERY - CHALLENGES AND OPPORTUNITIES M.J. Cardoso Breast Unit, Champalimaud Foundation, Lisbon, Portugal Locally advanced breast cancer (LABC) occurs at presentation in one fifth of breast cancer patients worldwide but with much lesser incidence in countries with established screening programs. LABC includes large operable primary breast tumors (stage IIB, IIIA) and/or those involving the skin or chest wall and/or those with extensive lymphadenopathy (stage IIIB, IIIC). A distinct form of LABC is inflammatory breast cancer (IBC). In summary LABC is a very heterogeneous entity with different biology cancers carrying however a common factor – a worse prognosis. For a long time mastectomy was the mainstay of treatment in those patients, however local recurrences were high (50%) and survival very low (2-5% OS). The addition of radiotherapy after surgery decreased loco-regional recurrences but survival remained very low. Adding systemic therapy to surgery and radiotherapy objectively improved outcomes. Currently a combination of systemic treatments with surgery and radiation is the standard of care in LABC due to improvement of loco-regional control and survival. Regarding loco-regional approach there are three main groups in LABC: large operable, inoperable and inflammatory tumors. Surgery after induction systemic therapy in LABC allows breast conservative surgery in variable percentages depending on tumor/ patient characteristics. Mastectomy remains the option before or after radiotherapy for those patients not amenable to conservation treatment and for all patients with IBC. Whenever mastectomy is possible patients should have the option to undergo either immediate (IBR) or delayed breast reconstruction. When IBR is considered major concerns are the risk of increased complications, compromised cosmesis and difficulties in planning radiotherapy even if there are no data from randomized trials confirming these potential issues. However, a minority of those patients remain inoperable, even after systemic therapy and radiotherapy, and represent one of the most difficult challenges to multidisciplinary teams. Salvage and debulking surgery have been described in a limited number of cases where local control remains the major concern. In this particular setting thoracic wall reconstruction, if feasible, is a necessity in the majority of interventions. Regarding axillary status and even after a complete clinical/imaging response with neo-adjuvant systemic therapy, clearance is the current recommendation after a positive pre-treatment staging and in IBC cancer. Treatment of LABC is a therapeutic challenge, encompassing a heterogeneous group of lesions, and treatment decisions must be undertaken understanding that in view of minor evidence from randomized studies most of the patients will be managed empirically supported by what should be a dedicated multidisciplinary expert approach. [1] Giordano SH. Update on locally advanced breast cancer. Oncologist. 2003;8(6):521-30 [2] Gonzalez-Angulo AM, Hennessy BT, Broglio K, Meric-Bernstam F, Cristofanilli M, Giordano SH, Buchholz TA, Sahin A, Singletary SE, Buzdar AU, Hortobágyi GN. Trends for inflammatory breast cancer: is survival improving? Oncologist. 2007 Aug;12(8):904-12 [3] Chia S, Swain SM, Byrd DR, Mankoff DA. Locally advanced and inflammatory breast cancer. J Clin Oncol. 2008 Feb 10;26(5):786-90 [4] Dawood S, Merajver SD, Viens P, Vermeulen PB, Swain SM, Buchholz TA, Dirix LY, Levine PH, Lucci A, Krishnamurthy S, Robertson FM, Woodward WA, Yang WT, Ueno NT, Cristofanilli M. International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Ann Oncol. 2011 Mar;22(3):515-23 [5] Cox C, Holloway CM, Shaheta A, Nofech-Mozes S, Wright FC. What is the burden of axillary disease after neoadjuvant therapy in women with locally advanced breast cancer? Curr Oncol. 2013 Apr;20(2):111-7