- Email: [email protected]
II Breast Cancer
3,602 women who were treated with either mastectomy (1,606 patients) or breast conservation therapy plus radiotherapy (1,996 patients). They reported 55 breast tumor recurrences in the mastectomy group (3.4%) and 117 in the breast conservation therapy group (5.8%). The emphasis of the article was the greater incidence of breast tumor recurrences in women younger than 35 years of age compared with the incidence in women older than 50 years of age (hazard ratio 2.34)—an observation that has also been reported by others. Breast cancer in young age groups is more frequently associated with high histologic grade and hormone receptor-negative status than in older women. The authors noted that a total of 2,743 patients re-
1–49
Ten-Year Multi-Institutional Results of Breast-Conserving Surgery and Radiotherapy in BRCA1/2-Associated Stage I/II Breast Cancer Pierce LJ, Levin AM, Rebbeck TR, et al (Univ of Michigan, Ann Arbor; Univ of Pennsylvania, Philadelphia; Univ of Utah School of Medicine, Salt Lake City; et al) J Clin Oncol 24:2437-2443, 2006
Purpose.—We compared the outcome of breast-conserving surgery and radiotherapy in BRCA1/2 mutation carriers with breast cancer versus that of matched sporadic controls. Methods.—A total of 160 BRCA1/2 mutation carriers with breast cancer were matched with 445 controls with sporadic breast cancer. Primary end points were rates of in-breast tumor recurrence
84 84
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ceived adjuvant radiotherapy, which indicates that if all 1,996 patients treated with breast conservation therapy received radiotherapy, then the other 747 women who received radiotherapy were treated with mastectomy. It is not possible to determine how many of the 176 women younger than 35 years of age were treated with mastectomy versus breast conservation or how many received radiotherapy. Furthermore, the authors did not analyze the impact that a boost of irradiation has in reducing the incidence of breast tumor recurrences, particularly in young patients, which has been analyzed by Bartelink and colleagues1 in a randomized EORTC study. We agree with the authors that young age does place women at a higher
risk of breast tumor recurrence, but this risk is associated with other prognostic factors and is also influenced by the treatment techniques used. Close monitoring of young women with these risk indicators is critical to the early detection of breast tumor recurrence, which can be successfully treated in many instances.
(IBTR) and contralateral breast cancers (CBCs). Median follow-up was 7.9 years for mutation carriers and 6.7 years for controls. Results.—There was no significant difference in IBTR overall between carriers and controls; 10- and 15-year estimates were 12% and 24% for carriers and 9% and 17% for controls, respectively (hazard ratio [HR], 1.37; P = .19). Multivariate analyses for IBTR found BRCA1/2 mutation status to be an independent predictor of IBTR when carriers who had undergone oophorectomy were removed from analysis (HR, 1.99; P = .04); the incidence of IBTR in carriers who had undergone oophorectomy was not significantly different from that in sporadic controls (P = .37). CBCs were significantly greater in carriers versus controls, with 10- and 15-year estimates of 26% and 39% for carriers and 3% and 7% for controls, respectively (HR, 10.43;
P < .0001). Tamoxifen use significantly reduced risk of CBCs in mutation carriers (HR, 0.31; P = .05). Conclusion.—IBTR risk at 10 years is similar in BRCA1/2 carriers treated with breast conservation surgery who undergo oophorectomy versus sporadic controls. As expected, CBCs are significantly increased in carriers. Although the incidence of CBCs was significantly reduced in mutation carriers who received tamoxifen, this rate remained significantly greater than in controls. Additional strategies are needed to reduce contralateral cancers in these high-risk women.
Breast Diseases: A Year Book Quarterly Vol 18 No 1 2007
C. A. Perez, MD
Reference 1. Bartelink H, Horiot JC, Poortmans P, et al: Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med 345:1378-1387, 2001.
Approximately 5% of all women diagnosed with breast cancer harbor a germline mutation in the BRCA1 or BRCA2 gene. If these women opt for breast-conserving surgery, prior studies have indicated that the long-term risk of a second primary ipsilateral or
contralateral breast cancer may exceed 50%.1 In contrast, this landmark study by Pierce and colleagues strongly suggested that for women with BRCA1/2associated breast cancer who undergo breast-conserving surgery, a secondary prevention strategy including both oophorectomy and adjuvant endocrine therapy lowers the risk of second primary ipsilateral and contralateral breast cancer to a much more acceptable level. It is notable that this secondary prevention strategy appears to be beneficial even among women with hormone receptor-negative tumors. In addition to its clinical implications, this study raises some interesting questions about the radiobiology of
1–50
Local Recurrences After Conservative Treatment of Ductal Carcinoma-In-Situ of the Breast Without Radiotherapy: The Effect of Age van der Velden AP, Peeters PH, Koot VC, et al (Univ Med Centre Utrecht, The Netherlands; Comprehensive Cancer Centre Middle Netherlands, Utrecht) Ann Surg Oncol 13:990-998, 2006
Background.—The main goal in treatment of ductal carcinoma-in-situ (DCIS) of the breast is to prevent local recurrences. Radiotherapy after breastconserving surgery has been shown to decrease the recurrence rate, although whether all patients should be treated with radiotherapy remains a topic of debate. The aim of this study was to assess the local recurrence rate after conserva-
BRCA1/2-associated breast cancers. Because BRCA1 and BRCA2 are involved in the repair of double-stranded DNA breaks, it is possible that individuals with BRCA1/2 mutations may manifest a radiosensitive phenotype with regard to primary-tumor control, normal-tissue reactions, and radiationinduced carcinogenesis. The data from the current study suggested that BRCA1/2-associated breast cancers might be more radiosensitive than sporadic breast cancers, because recurrences of the primary tumor in the initially involved quadrant were less common among BRCA1/2 cases than among sporadic controls. If confirmed, this finding could have implications for
the optimal radiotherapy dose and volume used in the treatment of BRCA1/2associated cancers. This study was not designed to assess radiation-related normal tissue reactions and carcinogenesis in women with BRCA1/2 mutations; further research in these areas is clearly needed.
tive surgical treatment of DCIS without radiotherapy and to identify risk factors for local recurrence. Methods.—A total of 499 female patients with 502 DCIS lesions treated in the period 1989 to 2002 were retrospectively reviewed. Survival rates were calculated by the Kaplan-Meier method, and differences were tested by using the log-rank test. The association of variables with local recurrence was analyzed by using the χ2 test. Results.—Treatment constituted of lumpectomy in 329 patients (65%). Thirty-eight patients (8%) had diseasepositive margins, and for 41 patients (8%) the margin status was not known. Eighty tumors recurred, for a local recurrence rate of 13% after 4 years compared with 17% for patients treated with breastconserving surgery only. Risk factors for ipsilateral recurrences were younger age (< 50 years), treatment with breast-
conserving surgery only, and presence of disease-involved surgical margins. Conclusions.—Conservative treatment of DCIS results in high recurrences rates, and outcomes can be improved by performing more radical surgery. Because radiotherapy has been shown to be effective in preventing recurrent disease, and, to date, no subgroups have been identified in which radiation can be omitted, its use is recommended, especially in younger patients.
B. D. Smith, MD
Reference 1. Haffty BG, Harrold E, Khan AJ, et al: Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status. Lancet 359:1471-1477, 2002.
For women with DCIS, age at diagnosis is inversely correlated with risk of local recurrence. This observation leads to 2 important clinical questions. First, is there a group of younger women for whom mastectomy should be favored over conservative surgery plus radiotherapy (CS+RT) simply because of their young age? Second, is a there a group
®
Breast Diseases: A Year Book Quarterly Vol 18 No 1 2007
85 85
1–49
Ten-Year Multi-Institutional Results of Breast-Conserving Surgery and Radiotherapy in BRCA1/2-Associated Stage I/II Breast Cancer Pierce LJ, Levin AM, Rebbeck TR, et al (Univ of Michigan, Ann Arbor; Univ of Pennsylvania, Philadelphia; Univ of Utah School of Medicine, Salt Lake City; et al) J Clin Oncol 24:2437-2443, 2006
Purpose.—We compared the outcome of breast-conserving surgery and radiotherapy in BRCA1/2 mutation carriers with breast cancer versus that of matched sporadic controls. Methods.—A total of 160 BRCA1/2 mutation carriers with breast cancer were matched with 445 controls with sporadic breast cancer. Primary end points were rates of in-breast tumor recurrence
84 84
®
ceived adjuvant radiotherapy, which indicates that if all 1,996 patients treated with breast conservation therapy received radiotherapy, then the other 747 women who received radiotherapy were treated with mastectomy. It is not possible to determine how many of the 176 women younger than 35 years of age were treated with mastectomy versus breast conservation or how many received radiotherapy. Furthermore, the authors did not analyze the impact that a boost of irradiation has in reducing the incidence of breast tumor recurrences, particularly in young patients, which has been analyzed by Bartelink and colleagues1 in a randomized EORTC study. We agree with the authors that young age does place women at a higher
risk of breast tumor recurrence, but this risk is associated with other prognostic factors and is also influenced by the treatment techniques used. Close monitoring of young women with these risk indicators is critical to the early detection of breast tumor recurrence, which can be successfully treated in many instances.
(IBTR) and contralateral breast cancers (CBCs). Median follow-up was 7.9 years for mutation carriers and 6.7 years for controls. Results.—There was no significant difference in IBTR overall between carriers and controls; 10- and 15-year estimates were 12% and 24% for carriers and 9% and 17% for controls, respectively (hazard ratio [HR], 1.37; P = .19). Multivariate analyses for IBTR found BRCA1/2 mutation status to be an independent predictor of IBTR when carriers who had undergone oophorectomy were removed from analysis (HR, 1.99; P = .04); the incidence of IBTR in carriers who had undergone oophorectomy was not significantly different from that in sporadic controls (P = .37). CBCs were significantly greater in carriers versus controls, with 10- and 15-year estimates of 26% and 39% for carriers and 3% and 7% for controls, respectively (HR, 10.43;
P < .0001). Tamoxifen use significantly reduced risk of CBCs in mutation carriers (HR, 0.31; P = .05). Conclusion.—IBTR risk at 10 years is similar in BRCA1/2 carriers treated with breast conservation surgery who undergo oophorectomy versus sporadic controls. As expected, CBCs are significantly increased in carriers. Although the incidence of CBCs was significantly reduced in mutation carriers who received tamoxifen, this rate remained significantly greater than in controls. Additional strategies are needed to reduce contralateral cancers in these high-risk women.
Breast Diseases: A Year Book Quarterly Vol 18 No 1 2007
C. A. Perez, MD
Reference 1. Bartelink H, Horiot JC, Poortmans P, et al: Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med 345:1378-1387, 2001.
Approximately 5% of all women diagnosed with breast cancer harbor a germline mutation in the BRCA1 or BRCA2 gene. If these women opt for breast-conserving surgery, prior studies have indicated that the long-term risk of a second primary ipsilateral or
contralateral breast cancer may exceed 50%.1 In contrast, this landmark study by Pierce and colleagues strongly suggested that for women with BRCA1/2associated breast cancer who undergo breast-conserving surgery, a secondary prevention strategy including both oophorectomy and adjuvant endocrine therapy lowers the risk of second primary ipsilateral and contralateral breast cancer to a much more acceptable level. It is notable that this secondary prevention strategy appears to be beneficial even among women with hormone receptor-negative tumors. In addition to its clinical implications, this study raises some interesting questions about the radiobiology of
1–50
Local Recurrences After Conservative Treatment of Ductal Carcinoma-In-Situ of the Breast Without Radiotherapy: The Effect of Age van der Velden AP, Peeters PH, Koot VC, et al (Univ Med Centre Utrecht, The Netherlands; Comprehensive Cancer Centre Middle Netherlands, Utrecht) Ann Surg Oncol 13:990-998, 2006
Background.—The main goal in treatment of ductal carcinoma-in-situ (DCIS) of the breast is to prevent local recurrences. Radiotherapy after breastconserving surgery has been shown to decrease the recurrence rate, although whether all patients should be treated with radiotherapy remains a topic of debate. The aim of this study was to assess the local recurrence rate after conserva-
BRCA1/2-associated breast cancers. Because BRCA1 and BRCA2 are involved in the repair of double-stranded DNA breaks, it is possible that individuals with BRCA1/2 mutations may manifest a radiosensitive phenotype with regard to primary-tumor control, normal-tissue reactions, and radiationinduced carcinogenesis. The data from the current study suggested that BRCA1/2-associated breast cancers might be more radiosensitive than sporadic breast cancers, because recurrences of the primary tumor in the initially involved quadrant were less common among BRCA1/2 cases than among sporadic controls. If confirmed, this finding could have implications for
the optimal radiotherapy dose and volume used in the treatment of BRCA1/2associated cancers. This study was not designed to assess radiation-related normal tissue reactions and carcinogenesis in women with BRCA1/2 mutations; further research in these areas is clearly needed.
tive surgical treatment of DCIS without radiotherapy and to identify risk factors for local recurrence. Methods.—A total of 499 female patients with 502 DCIS lesions treated in the period 1989 to 2002 were retrospectively reviewed. Survival rates were calculated by the Kaplan-Meier method, and differences were tested by using the log-rank test. The association of variables with local recurrence was analyzed by using the χ2 test. Results.—Treatment constituted of lumpectomy in 329 patients (65%). Thirty-eight patients (8%) had diseasepositive margins, and for 41 patients (8%) the margin status was not known. Eighty tumors recurred, for a local recurrence rate of 13% after 4 years compared with 17% for patients treated with breastconserving surgery only. Risk factors for ipsilateral recurrences were younger age (< 50 years), treatment with breast-
conserving surgery only, and presence of disease-involved surgical margins. Conclusions.—Conservative treatment of DCIS results in high recurrences rates, and outcomes can be improved by performing more radical surgery. Because radiotherapy has been shown to be effective in preventing recurrent disease, and, to date, no subgroups have been identified in which radiation can be omitted, its use is recommended, especially in younger patients.
B. D. Smith, MD
Reference 1. Haffty BG, Harrold E, Khan AJ, et al: Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status. Lancet 359:1471-1477, 2002.
For women with DCIS, age at diagnosis is inversely correlated with risk of local recurrence. This observation leads to 2 important clinical questions. First, is there a group of younger women for whom mastectomy should be favored over conservative surgery plus radiotherapy (CS+RT) simply because of their young age? Second, is a there a group
®
Breast Diseases: A Year Book Quarterly Vol 18 No 1 2007
85 85