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Breast Conservation Therapy: The Influence of Molecular Subtype and Margins
after neoadjuvant chemotherapy. Cancer. 2005;103:689-695. 4. Chen AM, Meric-Bernstam F, Hunt KK, et al. Breast conservation after neoadjuvant chemotherapy: the
Breast Conservation Therapy: The Influence of Molecular Subtype and Margins Demirci S, Broadwater G, Marks LB, et al (Duke Univ Med Ctr, Durham, NC; Duke Cancer Inst, Durham, NC; Univ of North Carolina School of Medicine, Chapel Hill) Int J Radiat Oncol Biol Phys 83:814-820, 2012
Purpose.dTo evaluate treatment results and prognostic factors, especially margin status and molecular subtype, in early-stage breast cancer patients treated with breast conservation therapy (BCT). Methods and Materials.dThe records of 1,058 Stage I or II breast cancer patients treated with BCT (surgical excision plus radiotherapy) at Duke University Medical Center, Durham, North Carolina, from 1985e2005 were retrospectively reviewed. Conventional receptor analyses were used as surrogate markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal like). Actuarial estimates of overall survival (OS), cause-specific survival (CSS), failure-free survival, and locoregional control (LRC) were computed by use of Kaplan-Meier plots. We analyzed prognostic variables for significance using Cox proportional hazards univariate and multivariate analysis. The study was approved by the Duke University Medical Center Institutional Review Board. Results.dThe median age of the patients was 56 years (range, 18e 89 years). Of the patients, 80% had T1
102
MD Anderson Cancer Center experience. J Clin Oncol. 2004;22: 2303-2312.
Predictive factors for local recurrence in breast cancer. Semin Radiat Oncol. 2012;22:100-107.
5. van der Leij F, Elkhuizen PH, Bartelink H, van de Vijver MJ.
disease and 66% N0 disease pathologically. With a median follow-up of 9.8 years, an in-breast recurrence developed in 53 patients and 10 patients had nodal failure. For all patients, the 10year CSS rate was 94%; LRC rate, 94%; and failure-free survival rate, 88%. Luminal A patients had a CSS rate of 95% and LRC rate of 99%. Basal-type patients appeared to do worse, with regard to both CSS rate (74%) and LRC rate (76%), but the numbers were small and the difference was not statistically significant. LRC rates of patients with negative margins (widely negative, close, and extent of margin not known) were virtually identical (93%, 96%, and 94%, respectively). Those with positive margins appeared to fare slightly worse based on LRC rate (88%), but again, the numbers were small and the difference was not statistically significant. Conclusions.dBCT remains the treatment of choice for early-stage breast cancer patients irrespective of molecular subtype. Negative margins of excision are desirable, but the width of the negative margin does not influence outcome. In this article, Demirci and colleagues present a retrospective study examining the effect of molecular subtype and margin status on clinical outcomes in patients who underwent BCT for early-stage breast cancer. This very large series demonstrated excellent rates of LRC for all molecular subtypes. Although the rate of LRC was slightly lower for patients
Breast Diseases: A Year BookÒ Quarterly Vol 24 No 1 2013
with basal-type tumors (74%) than for patients with luminal A tumors (99%), this difference was not statistically significant. The effect of breast cancer subtype on LRC has been debated, particularly in the setting of earlystage breast cancer. This series contributes to the data suggesting that LRC is likely to be lower for patients with basal-type tumors but that, nonetheless, the rates of LRC are very high overall in the setting of BCT for early-stage breast cancer. As the authors point out, it is important to recognize that there are discrepancies between molecular subtyping based on gene expression profiling and approximations made via receptor status. The terminology for receptor subtype also varies relatively widely, in particular with respect to the term “luminal B.” In this series, luminal B was defined as estrogen receptor positive and/or progesterone receptor positive and human epidermal growth factor 2 (HER2) positive. Interestingly, the rate of LRC in patients with known HER2-positive status (luminal B and HER2-positive subtypes) was 100% in this series. The authors did not specify the type of chemotherapy used, but given the treatment era, the majority of patients with HER2-positive tumors likely did not receive HER2-targeted therapy; HER2-positive cancers not treated with HER2-targeted agents have generally been associated with lower rates of LRC. The use of systemic therapy did affect LRC in this series but was not analyzed by breast cancer subtype.
The other significant finding in this series is that the width of the negative surgical margin did not affect LRC. The importance of margin status has been debated in the setting of invasive breast cancer, and this series provides additional support to the growing body of evidence that suggests that while obtaining negative margins is likely to result in better LRC, the width of the margin does not affect LRC in the setting of BCT.
Overall, the very high rates of LRC demonstrated in this large single-institution series are encouraging and confirm the efficacy of BCT in the setting of negative margins of any width for all breast cancer subtypes. Given the advancements made in systemic therapy since this series was concluded, these rates of LRC are likely to further improve over time, but the gap in LRC may widen between basal-type tumors and others,
given the lack of targeted systemic therapy for these tumors. Nonetheless, as this series demonstrates, BCT remains an excellent option for the majority of patients with early-stage breast cancer, even those with basaltype tumors. A. Dosch, BS J. Wright, MD
Breast Diseases: A Year BookÒ Quarterly Vol 24 No 1 2013
103
Breast Conservation Therapy: The Influence of Molecular Subtype and Margins Demirci S, Broadwater G, Marks LB, et al (Duke Univ Med Ctr, Durham, NC; Duke Cancer Inst, Durham, NC; Univ of North Carolina School of Medicine, Chapel Hill) Int J Radiat Oncol Biol Phys 83:814-820, 2012
Purpose.dTo evaluate treatment results and prognostic factors, especially margin status and molecular subtype, in early-stage breast cancer patients treated with breast conservation therapy (BCT). Methods and Materials.dThe records of 1,058 Stage I or II breast cancer patients treated with BCT (surgical excision plus radiotherapy) at Duke University Medical Center, Durham, North Carolina, from 1985e2005 were retrospectively reviewed. Conventional receptor analyses were used as surrogate markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal like). Actuarial estimates of overall survival (OS), cause-specific survival (CSS), failure-free survival, and locoregional control (LRC) were computed by use of Kaplan-Meier plots. We analyzed prognostic variables for significance using Cox proportional hazards univariate and multivariate analysis. The study was approved by the Duke University Medical Center Institutional Review Board. Results.dThe median age of the patients was 56 years (range, 18e 89 years). Of the patients, 80% had T1
102
MD Anderson Cancer Center experience. J Clin Oncol. 2004;22: 2303-2312.
Predictive factors for local recurrence in breast cancer. Semin Radiat Oncol. 2012;22:100-107.
5. van der Leij F, Elkhuizen PH, Bartelink H, van de Vijver MJ.
disease and 66% N0 disease pathologically. With a median follow-up of 9.8 years, an in-breast recurrence developed in 53 patients and 10 patients had nodal failure. For all patients, the 10year CSS rate was 94%; LRC rate, 94%; and failure-free survival rate, 88%. Luminal A patients had a CSS rate of 95% and LRC rate of 99%. Basal-type patients appeared to do worse, with regard to both CSS rate (74%) and LRC rate (76%), but the numbers were small and the difference was not statistically significant. LRC rates of patients with negative margins (widely negative, close, and extent of margin not known) were virtually identical (93%, 96%, and 94%, respectively). Those with positive margins appeared to fare slightly worse based on LRC rate (88%), but again, the numbers were small and the difference was not statistically significant. Conclusions.dBCT remains the treatment of choice for early-stage breast cancer patients irrespective of molecular subtype. Negative margins of excision are desirable, but the width of the negative margin does not influence outcome. In this article, Demirci and colleagues present a retrospective study examining the effect of molecular subtype and margin status on clinical outcomes in patients who underwent BCT for early-stage breast cancer. This very large series demonstrated excellent rates of LRC for all molecular subtypes. Although the rate of LRC was slightly lower for patients
Breast Diseases: A Year BookÒ Quarterly Vol 24 No 1 2013
with basal-type tumors (74%) than for patients with luminal A tumors (99%), this difference was not statistically significant. The effect of breast cancer subtype on LRC has been debated, particularly in the setting of earlystage breast cancer. This series contributes to the data suggesting that LRC is likely to be lower for patients with basal-type tumors but that, nonetheless, the rates of LRC are very high overall in the setting of BCT for early-stage breast cancer. As the authors point out, it is important to recognize that there are discrepancies between molecular subtyping based on gene expression profiling and approximations made via receptor status. The terminology for receptor subtype also varies relatively widely, in particular with respect to the term “luminal B.” In this series, luminal B was defined as estrogen receptor positive and/or progesterone receptor positive and human epidermal growth factor 2 (HER2) positive. Interestingly, the rate of LRC in patients with known HER2-positive status (luminal B and HER2-positive subtypes) was 100% in this series. The authors did not specify the type of chemotherapy used, but given the treatment era, the majority of patients with HER2-positive tumors likely did not receive HER2-targeted therapy; HER2-positive cancers not treated with HER2-targeted agents have generally been associated with lower rates of LRC. The use of systemic therapy did affect LRC in this series but was not analyzed by breast cancer subtype.
The other significant finding in this series is that the width of the negative surgical margin did not affect LRC. The importance of margin status has been debated in the setting of invasive breast cancer, and this series provides additional support to the growing body of evidence that suggests that while obtaining negative margins is likely to result in better LRC, the width of the margin does not affect LRC in the setting of BCT.
Overall, the very high rates of LRC demonstrated in this large single-institution series are encouraging and confirm the efficacy of BCT in the setting of negative margins of any width for all breast cancer subtypes. Given the advancements made in systemic therapy since this series was concluded, these rates of LRC are likely to further improve over time, but the gap in LRC may widen between basal-type tumors and others,
given the lack of targeted systemic therapy for these tumors. Nonetheless, as this series demonstrates, BCT remains an excellent option for the majority of patients with early-stage breast cancer, even those with basaltype tumors. A. Dosch, BS J. Wright, MD
Breast Diseases: A Year BookÒ Quarterly Vol 24 No 1 2013
103