EDITORIAL Mastectomy May Be an Inferior Oncologic Approach Compared to Breast Preservation Lawrence B. Marks, MD, FASTRO,* Gaorav P. Gupta, MD, PhD,* Hyman B. Muss, MD, y and David W. Ollila, MD z Departments of *Radiation Oncology, y Medicine, and z Surgery, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina Received May 25, 2018, and in revised form Jul 16, 2018. Accepted for publication Jul 30, 2018. Multiple randomized studies have demonstrated that breast- conserving therapy (partial mastectomy plus whole breast radiation) can yield survival outcomes equivalent to those of mastectomy (1). However, newer population-based data suggest that breast cancerespecific survival and overall survival with breast-conserving therapy may actually be better than those with mastectomy (2-8). How is this possible? How can removal of the breast yield outcomes inferior to those of a therapy that leaves most of the breast intact and where in-breast failures are reported to occur in approximately 5% to 10% of patients at 10 years post- treatment in historical series (1) (albeit with lower rates over time (9), especially in favorable patients (10))? One possible explanation is that local control simply does not always matterdthat survival is usually dictated by systemic disease and is largely independent of local con- trol. This certainly is part of the explanation; improvements in local control do not necessarily readily translate into equivalent improvements in overall survival (1). Further- more, those who experience a local failure after breast- conservation therapy typically undergo a delayed salvage mastectomy, potentially compensating for their “subopti- mal” initial therapy. However, these are unlikely to be the only explanations because improvements in local control are associated with improvements in overall survival in both postlumpectomy and postmastectomy settings (1). Certainly, surgery does provide superior local control compared with radiation within resected tissues. Therefore, there must be factors that counterbalance this advantage of surgery, and we submit that this balance relates to the volume of treated tissue (Fig. 1). Traditional tangential breast radiation fields treat a larger volume (eg, more breast, skin, muscle, lymphatics) than mastectomy. With breast-conserving therapy, the lesser local control within the tissues that otherwise would have been resected with mastectomy is balanced (ie, compensated for) by the anti- tumor effects in the broader irradiated volume. If our un- derstanding of a balance is correct, how might recent changes in breast cancer care affect this balance? Remember, the classic studies of mastectomy versus breast conservation therapy were largely conducted in the 1970s to 1990s. So, let us briefly highlight some changes in breast cancer management since then. Improvements in breast imaging (eg, better defining the extent of the index lesion, better detection of multicentric disease) provide more careful selection of patients for breast preservation. There is also more consistent and careful pathologic attention to partial mastectomy margins, which has likely increased the local tumor control rates with breast conservation. Similarly, the wider adoption of 3-dimensional radiation treatment planning has likely increased the degree of coverage of the targeted residual breast tissue (and better sparing of nontarget adjacent normal tissues). In concert, these improvements in patient selection and pathologic margin assessment and the wider use of 3-dimensional radiation treatment planning have Reprint requests to: Lawrence B. Marks, MD, FASTRO, CB #7512, 101 Manning Dr, Chapel Hill, North Carolina 27599-7512. Tel: (984) 974- 0400; E-mail: [email protected] Conflict of interest: none. Int J Radiation Oncol Biol Phys, Vol. 103, No. 1, pp. 78e80, 2019 0360-3016/$ - see front matter Ó 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.ijrobp.2018.07.2021 Radiation Oncology International Journal of biology physics www.redjournal.org
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Mastectomy May Be an Inferior Oncologic Approach Compared to Breast Preservationwww.redjournal.org
EDITORIAL
Mastectomy May Be an Inferior Oncologic Approach Compared to Breast Preservation Lawrence B. Marks, MD, FASTRO,* Gaorav P. Gupta, MD, PhD,* Hyman B. Muss, MD,y and David W. Ollila, MDz
Departments of *Radiation Oncology, yMedicine, and zSurgery, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina
Received May 25, 2018, and in revised form Jul 16, 2018. Accepted for publication Jul 30, 2018.
Multiple randomized studies have demonstrated that breast- conserving therapy (partial mastectomy plus whole breast radiation) can yield survival outcomes equivalent to those of mastectomy (1). However, newer population-based data suggest that breast cancerespecific survival and overall survival with breast-conserving therapy may actually be better than those with mastectomy (2-8). How is this possible? How can removal of the breast yield outcomes inferior to those of a therapy that leaves most of the breast intact and where in-breast failures are reported to occur in approximately 5% to 10% of patients at 10 years post- treatment in historical series (1) (albeit with lower rates over time (9), especially in favorable patients (10))?
One possible explanation is that local control simply does not always matterdthat survival is usually dictated by systemic disease and is largely independent of local con- trol. This certainly is part of the explanation; improvements in local control do not necessarily readily translate into equivalent improvements in overall survival (1). Further- more, those who experience a local failure after breast- conservation therapy typically undergo a delayed salvage mastectomy, potentially compensating for their “subopti- mal” initial therapy. However, these are unlikely to be the only explanations because improvements in local control are associated with improvements in overall survival in both postlumpectomy and postmastectomy settings (1).
Certainly, surgery does provide superior local control compared with radiation within resected tissues. Therefore,
Reprint requests to: Lawrence B. Marks, MD, FASTRO, CB #7512,
101 Manning Dr, Chapel Hill, North Carolina 27599-7512. Tel: (984) 974-
0400; E-mail: [email protected]
Int J Radiation Oncol Biol Phys, Vol. 103, No. 1, pp. 78e80, 2019 0360-3016/$ - see front matter 2018 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.ijrobp.2018.07.2021
there must be factors that counterbalance this advantage of surgery, and we submit that this balance relates to the volume of treated tissue (Fig. 1). Traditional tangential breast radiation fields treat a larger volume (eg, more breast, skin, muscle, lymphatics) than mastectomy. With breast-conserving therapy, the lesser local control within the tissues that otherwise would have been resected with mastectomy is balanced (ie, compensated for) by the anti- tumor effects in the broader irradiated volume. If our un- derstanding of a balance is correct, how might recent changes in breast cancer care affect this balance? Remember, the classic studies of mastectomy versus breast conservation therapy were largely conducted in the 1970s to 1990s. So, let us briefly highlight some changes in breast cancer management since then.
Improvements in breast imaging (eg, better defining the extent of the index lesion, better detection of multicentric disease) provide more careful selection of patients for breast preservation. There is also more consistent and careful pathologic attention to partial mastectomy margins, which has likely increased the local tumor control rates with breast conservation. Similarly, the wider adoption of 3-dimensional radiation treatment planning has likely increased the degree of coverage of the targeted residual breast tissue (and better sparing of nontarget adjacent normal tissues). In concert, these improvements in patient selection and pathologic margin assessment and the wider use of 3-dimensional radiation treatment planning have
Conflict of interest: none.
Volume 103 Number 1 2019 Mastectomy compared with breast preservation 79
likely increased the effectiveness of partial mastectomy and whole breast irradiation and improved outcomes.
With mastectomy, many of the recent advances have been to reduce the extent of surgery (eg, skin/nipple- sparing mastectomy in lieu of more traditional mastec- tomies). Although these approaches are certainly appro- priate and have been validated (11), it is possible that this lesser surgical therapy is associated with a small increase in local failure and worse outcomes. This might be especially true as these approaches are applied more broadly (and perhaps among patients with less favorable characteristics than the patients in the studies in which these approaches were tested). Furthermore, these relatively newer mastec- tomy techniques may not undergo the pathologic scrutiny that partial mastectomy specimens undergo. For example, the nipple margin gets a very focused pathologic evaluation (12), but the remainder of the mastectomy specimen has a random sampling of the margins, and there is variation in the thickness of mastectomy flaps (13). Ideally, the flaps would be created in the subcutaneous plane between the dermis and breast parenchyma.
In a recent issue of the Red Journal, Giannotti et al report the results of an elegant analysis using magnetic resonance imaging to better quantify the variation in skin flap thickness in 501 postmastectomy breasts (in 367 women; mostly with breast cancer, but also including some undergoing elective/prophylactic surgery) (14). They demonstrate that skin flap thickness varies by location (thinner in the central [mean z 6-10 mm] vs peripheral [mean z 14-24 mm] regions of the breast), and there is much interpatient variation (eg, standard deviations range from z 6-14 mm for the different regions; personal communication with the authors, July 2018). Furthermore, the incidence of visualizing residual breast tissue increases
with skin flap thickness and is seen in 3% of breasts after total mastectomy, 13% after skin-sparing mastectomy, and >50% after nipple-sparing mastectomy (with similar data in those undergoing prophylactic vs therapeutic mastec- tomy; personal communication with the authors, July 2018). Thus, the increasing use of skin-sparing and nipple- sparing techniques, with associated increases in residual breast tissue, and the nonstandard approach to the patho- logic evaluation of margins, may be reducing the efficacy of mastectomy.
Breast-conserving therapy and mastectomy also differ in the use of adjuvant radiation therapy (RT) for patients with pathologic N1 disease. Despite prospective randomized evidence demonstrating a benefit for postmastectomy RT in patients with 1 to 3 positive axillary lymph nodes, it is not routinely recommended. Considerations such as a low volume of axillary metastases, high number of axillary lymph nodes removed, and additional radiation morbidity in patients who underwent immediate breast reconstruction may drive decisions to withhold postmastectomy RT in lymph nodeepositive patients. In contrast, N1 patients who undergo lumpectomy are almost universally recommended adjuvant whole-breast RT (that will incidentally include the lower/lateral aspect of the axilla), frequently also with regional nodal fields. Elective regional nodal RT has recently been demonstrated to improve disease-free and metastases-free survival in 2 prospective randomized trials (15, 16).
Similarly, the move toward sentinel lymph node biopsy (SLNB) may have different implications for breast con- servation (in which tangential RT fields routinely inciden- tally include the low axilla, hence mitigating the small but nonzero risk of a false-negative SLNB) versus mastectomy (in which the axilla typically receives no further direct therapy after a negative SLNB).
Collectively, these changes in how breast conservation and mastectomy are performed may have altered the bal- ance that led to the equivalent outcomes with these 2 ap- proaches seen in the classic randomized trials. We suggest that adjuvant RT may have a more important role when surgical practice evolves to reduce the volume of tissue resected during breast and axillary surgery. The integral role of adjuvant RT in breast-conserving therapy may explain why it is associated with better breast cancerespecific survival and overall survival relative to mastectomy in several recent population-based studies (2- 8). This improvement in survival is strongest in early- stage subgroups (in which postmastectomy RT is seldom used) and in those with comorbiditiesdfor whom systemic chemotherapy is less often applied (2, 4, 8)dsuggesting possible multimodality interactions.
Systemic therapies can also affect local control and certainly may affect the need for, and the impact of, different local therapies. Any differences in the anticancer outcomes of varying local approaches might be diluted (or totally negated) by increasingly-efficacious systemic
Marks et al. International Journal of Radiation Oncology Biology Physics80
therapies. For example, the proliferation of efficacious therapies for hormone-positive and human epidermal growth factor receptor 2 (HER2)eamplified cancers has improved outcomes. Furthermore, it is becoming increas- ingly clear that breast cancer represents a mosaic of sub- groups with different risks of local versus distant spread and differing responses to specific therapies (eg, HER2 positive vs negative cases, luminal vs basal) that may affect the utility of various local therapies. For example, patients with triple negative tumors might have an overall higher risk of local failure; thus, outcomes might be more sensitive to subtle reductions in local therapy. The changing land- scape of systemic therapies, and our evolving understand- ing of patient subgroups, may continually affect the relative merits of various local therapies.
In the face of continued improvement in systemic ther- apy and our emerging knowledge regarding biologically defined patient subsets, what are the lessons, if any, for our evolving locoregional therapies? First, care should be taken in reducing local therapies (eg, omitting postlumpectomy breast RT, using thicker mastectomy skin flaps for cosmetic considerations, omitting axillary therapy with a positive SLNB), especially in subsets of patients who are more susceptible to residual disease, such as those with a triple negative molecular phenotype or lymphovascular space invasion. Second, quality metrics to ensure adequate per- formance of procedures should be established and moni- tored; the skin-flap thickness data reported by Giannotti et al suggest that there is much variation presently. Third, patient selection, oncologic surgical technique, and margin assessment must be a mainstay for all oncologic surgical procedures, not just for patients undergoing breast- conserving therapy. Patients who choose skin-sparing or nipple-sparing mastectomy deserve an appropriate onco- logic resection and a thorough margin assessment, not just the nipple margin.
We are concerned that the equivalent survival achieved with mastectomy versus breast-conserving therapy has been perhaps misinterpreted to mean that we can safely reduce therapy. As discussed, breast-conserving therapy is not less therapy than mastectomy (eg, the treated volume is larger; Fig. 1), particularly in the modern era of less-extensive surgery. A greater understanding of why some patients with early stage breast cancer who are eligible for breast- conservation therapy choose to undergo mastectomy is needed. Almost paradoxically, we suspect that one of the driving factors may be fear of recurrence and a misguided belief that mastectomy may be a more “aggressive” treat- ment than breast conservation. We believe that patients should be informed that the opposite may very well be truedthat lumpectomy plus RT provides a greater volume of locoregional therapy and is associated with improved
clinical outcomes in modern population-based studies. Pa- tients will continue to need multidisciplinary evaluations with providers familiar with these issues to help make optimal care decisions.
References
1. Early Breast Cancer Trialists’ Collaborative Group. Effects of radio-
therapy and surgery in early breast cancer e An overview of the
randomized trials. N Engl J Med 1995;333:1444-1456.
2. Lagendijk M, van Maaren MC, Saadatmand S, et al. Breast conserving
therapy and mastectomy revisited: Breast cancer-specific survival and
the influence of prognostic factors in 129,692 patients. Int J Cancer
2018;142:165-175.
3. Agarwal S, Pappas L, Neumayer L, et al. Effect of breast conservation
therapy vs mastectomy on disease-specific survival for early-stage
breast cancer. JAMA Surg 2014;149:267-274.
4. Chen K, Liu J, Zhu L, et al. Comparative effectiveness study of breast-
conserving surgery and mastectomy in the general population: A
NCDB analysis. Oncotarget 2015;6:40127-40140.
5. Hwang ES, Lichtensztajn DY, Gomez SL, et al. Survival after lump-
ectomy and mastectomy for early stage invasive breast cancer. Cancer
2013;119:1402-1411.
6. Fisher S, Gao H, Yasui Y, et al. Survival in stage I-III breast cancer
patients by surgical treatment in a publicly funded health care system.
Ann Oncol 2015;26:1161-1169.
7. Hartmann-Johnsen OJ, Karesen R, Schlichting E, et al. Survival is
better after breast conserving therapy than mastectomy for early stage
breast cancer: A registry-based follow-up study of Norwegian women
primary operated between 1998 and 2008. Ann Surg Oncol 2015;22:
3836-3845.
8. van Marren MC, de Munck L, de Bock GH, et al. 10 year survival after
breast-conserving surgery plus radiotherapy compared with mastec-
tomy in early breast cancer in The Netherlands: A population-based
study. Lancet Oncol 2016;17:1158-1170.
9. van Laar C, van der Sangen MJ, Poortmans PM, et al. Local recur-
rence following breast-conserving treatment in women aged 40 years
or younger: Trends in risk and the impact on prognosis in a
population-based cohort of 1143 patients. Eur J Cancer 2013;49:
3093-3101.
10. Arvold ND, Taghian AG, Niemierko A, et al. Age, breast cancer
subtype approximation, and local recurrence after breast-conserving
therapy. J Clin Oncol 2011;29:3885-3891.
11. Smith BL, Tang R, Rai U, et al. Oncologic safety of nipple-sparing
mastectomy in women with breast cancer. J Am Coll Surg 2017;225:
361-365.
12. Tang R, Coopey SB, Merrill AL, et al. Positive nipple margins in
nipple-sparing mastectomies: Rates, management, and oncologic
safety. J Am Coll Surg 2016;222:1149-1155.
13. Robertson SA, Rusby JE, Cutress RI. Determinants of optimal mas-
tectomy skin flap thickness. Br J Surg 2014;101:899-911.
14. Giannotti DG, Hanna SA, Cerri GG, et al. Analysis of skin flap
thickness and residual breast tissue after mastectomy. Int J Radiat
Oncol Biol Phys 2018;102:82-91.
15. Poortmans PM, Collette S, Kirkove C, et al. Internal mammary and
medical supraclavicular irradiation in breast cancer. N Engl J Med
2015;373:317-327.
16. Whelan TJ, Olivottto IA, Parulekar WR, et al. Regional nodal irra-
diation in early-stage breast cancer. N Engl J Med 2015;373:307-316.
References
EDITORIAL
Mastectomy May Be an Inferior Oncologic Approach Compared to Breast Preservation Lawrence B. Marks, MD, FASTRO,* Gaorav P. Gupta, MD, PhD,* Hyman B. Muss, MD,y and David W. Ollila, MDz
Departments of *Radiation Oncology, yMedicine, and zSurgery, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina
Received May 25, 2018, and in revised form Jul 16, 2018. Accepted for publication Jul 30, 2018.
Multiple randomized studies have demonstrated that breast- conserving therapy (partial mastectomy plus whole breast radiation) can yield survival outcomes equivalent to those of mastectomy (1). However, newer population-based data suggest that breast cancerespecific survival and overall survival with breast-conserving therapy may actually be better than those with mastectomy (2-8). How is this possible? How can removal of the breast yield outcomes inferior to those of a therapy that leaves most of the breast intact and where in-breast failures are reported to occur in approximately 5% to 10% of patients at 10 years post- treatment in historical series (1) (albeit with lower rates over time (9), especially in favorable patients (10))?
One possible explanation is that local control simply does not always matterdthat survival is usually dictated by systemic disease and is largely independent of local con- trol. This certainly is part of the explanation; improvements in local control do not necessarily readily translate into equivalent improvements in overall survival (1). Further- more, those who experience a local failure after breast- conservation therapy typically undergo a delayed salvage mastectomy, potentially compensating for their “subopti- mal” initial therapy. However, these are unlikely to be the only explanations because improvements in local control are associated with improvements in overall survival in both postlumpectomy and postmastectomy settings (1).
Certainly, surgery does provide superior local control compared with radiation within resected tissues. Therefore,
Reprint requests to: Lawrence B. Marks, MD, FASTRO, CB #7512,
101 Manning Dr, Chapel Hill, North Carolina 27599-7512. Tel: (984) 974-
0400; E-mail: [email protected]
Int J Radiation Oncol Biol Phys, Vol. 103, No. 1, pp. 78e80, 2019 0360-3016/$ - see front matter 2018 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.ijrobp.2018.07.2021
there must be factors that counterbalance this advantage of surgery, and we submit that this balance relates to the volume of treated tissue (Fig. 1). Traditional tangential breast radiation fields treat a larger volume (eg, more breast, skin, muscle, lymphatics) than mastectomy. With breast-conserving therapy, the lesser local control within the tissues that otherwise would have been resected with mastectomy is balanced (ie, compensated for) by the anti- tumor effects in the broader irradiated volume. If our un- derstanding of a balance is correct, how might recent changes in breast cancer care affect this balance? Remember, the classic studies of mastectomy versus breast conservation therapy were largely conducted in the 1970s to 1990s. So, let us briefly highlight some changes in breast cancer management since then.
Improvements in breast imaging (eg, better defining the extent of the index lesion, better detection of multicentric disease) provide more careful selection of patients for breast preservation. There is also more consistent and careful pathologic attention to partial mastectomy margins, which has likely increased the local tumor control rates with breast conservation. Similarly, the wider adoption of 3-dimensional radiation treatment planning has likely increased the degree of coverage of the targeted residual breast tissue (and better sparing of nontarget adjacent normal tissues). In concert, these improvements in patient selection and pathologic margin assessment and the wider use of 3-dimensional radiation treatment planning have
Conflict of interest: none.
Volume 103 Number 1 2019 Mastectomy compared with breast preservation 79
likely increased the effectiveness of partial mastectomy and whole breast irradiation and improved outcomes.
With mastectomy, many of the recent advances have been to reduce the extent of surgery (eg, skin/nipple- sparing mastectomy in lieu of more traditional mastec- tomies). Although these approaches are certainly appro- priate and have been validated (11), it is possible that this lesser surgical therapy is associated with a small increase in local failure and worse outcomes. This might be especially true as these approaches are applied more broadly (and perhaps among patients with less favorable characteristics than the patients in the studies in which these approaches were tested). Furthermore, these relatively newer mastec- tomy techniques may not undergo the pathologic scrutiny that partial mastectomy specimens undergo. For example, the nipple margin gets a very focused pathologic evaluation (12), but the remainder of the mastectomy specimen has a random sampling of the margins, and there is variation in the thickness of mastectomy flaps (13). Ideally, the flaps would be created in the subcutaneous plane between the dermis and breast parenchyma.
In a recent issue of the Red Journal, Giannotti et al report the results of an elegant analysis using magnetic resonance imaging to better quantify the variation in skin flap thickness in 501 postmastectomy breasts (in 367 women; mostly with breast cancer, but also including some undergoing elective/prophylactic surgery) (14). They demonstrate that skin flap thickness varies by location (thinner in the central [mean z 6-10 mm] vs peripheral [mean z 14-24 mm] regions of the breast), and there is much interpatient variation (eg, standard deviations range from z 6-14 mm for the different regions; personal communication with the authors, July 2018). Furthermore, the incidence of visualizing residual breast tissue increases
with skin flap thickness and is seen in 3% of breasts after total mastectomy, 13% after skin-sparing mastectomy, and >50% after nipple-sparing mastectomy (with similar data in those undergoing prophylactic vs therapeutic mastec- tomy; personal communication with the authors, July 2018). Thus, the increasing use of skin-sparing and nipple- sparing techniques, with associated increases in residual breast tissue, and the nonstandard approach to the patho- logic evaluation of margins, may be reducing the efficacy of mastectomy.
Breast-conserving therapy and mastectomy also differ in the use of adjuvant radiation therapy (RT) for patients with pathologic N1 disease. Despite prospective randomized evidence demonstrating a benefit for postmastectomy RT in patients with 1 to 3 positive axillary lymph nodes, it is not routinely recommended. Considerations such as a low volume of axillary metastases, high number of axillary lymph nodes removed, and additional radiation morbidity in patients who underwent immediate breast reconstruction may drive decisions to withhold postmastectomy RT in lymph nodeepositive patients. In contrast, N1 patients who undergo lumpectomy are almost universally recommended adjuvant whole-breast RT (that will incidentally include the lower/lateral aspect of the axilla), frequently also with regional nodal fields. Elective regional nodal RT has recently been demonstrated to improve disease-free and metastases-free survival in 2 prospective randomized trials (15, 16).
Similarly, the move toward sentinel lymph node biopsy (SLNB) may have different implications for breast con- servation (in which tangential RT fields routinely inciden- tally include the low axilla, hence mitigating the small but nonzero risk of a false-negative SLNB) versus mastectomy (in which the axilla typically receives no further direct therapy after a negative SLNB).
Collectively, these changes in how breast conservation and mastectomy are performed may have altered the bal- ance that led to the equivalent outcomes with these 2 ap- proaches seen in the classic randomized trials. We suggest that adjuvant RT may have a more important role when surgical practice evolves to reduce the volume of tissue resected during breast and axillary surgery. The integral role of adjuvant RT in breast-conserving therapy may explain why it is associated with better breast cancerespecific survival and overall survival relative to mastectomy in several recent population-based studies (2- 8). This improvement in survival is strongest in early- stage subgroups (in which postmastectomy RT is seldom used) and in those with comorbiditiesdfor whom systemic chemotherapy is less often applied (2, 4, 8)dsuggesting possible multimodality interactions.
Systemic therapies can also affect local control and certainly may affect the need for, and the impact of, different local therapies. Any differences in the anticancer outcomes of varying local approaches might be diluted (or totally negated) by increasingly-efficacious systemic
Marks et al. International Journal of Radiation Oncology Biology Physics80
therapies. For example, the proliferation of efficacious therapies for hormone-positive and human epidermal growth factor receptor 2 (HER2)eamplified cancers has improved outcomes. Furthermore, it is becoming increas- ingly clear that breast cancer represents a mosaic of sub- groups with different risks of local versus distant spread and differing responses to specific therapies (eg, HER2 positive vs negative cases, luminal vs basal) that may affect the utility of various local therapies. For example, patients with triple negative tumors might have an overall higher risk of local failure; thus, outcomes might be more sensitive to subtle reductions in local therapy. The changing land- scape of systemic therapies, and our evolving understand- ing of patient subgroups, may continually affect the relative merits of various local therapies.
In the face of continued improvement in systemic ther- apy and our emerging knowledge regarding biologically defined patient subsets, what are the lessons, if any, for our evolving locoregional therapies? First, care should be taken in reducing local therapies (eg, omitting postlumpectomy breast RT, using thicker mastectomy skin flaps for cosmetic considerations, omitting axillary therapy with a positive SLNB), especially in subsets of patients who are more susceptible to residual disease, such as those with a triple negative molecular phenotype or lymphovascular space invasion. Second, quality metrics to ensure adequate per- formance of procedures should be established and moni- tored; the skin-flap thickness data reported by Giannotti et al suggest that there is much variation presently. Third, patient selection, oncologic surgical technique, and margin assessment must be a mainstay for all oncologic surgical procedures, not just for patients undergoing breast- conserving therapy. Patients who choose skin-sparing or nipple-sparing mastectomy deserve an appropriate onco- logic resection and a thorough margin assessment, not just the nipple margin.
We are concerned that the equivalent survival achieved with mastectomy versus breast-conserving therapy has been perhaps misinterpreted to mean that we can safely reduce therapy. As discussed, breast-conserving therapy is not less therapy than mastectomy (eg, the treated volume is larger; Fig. 1), particularly in the modern era of less-extensive surgery. A greater understanding of why some patients with early stage breast cancer who are eligible for breast- conservation therapy choose to undergo mastectomy is needed. Almost paradoxically, we suspect that one of the driving factors may be fear of recurrence and a misguided belief that mastectomy may be a more “aggressive” treat- ment than breast conservation. We believe that patients should be informed that the opposite may very well be truedthat lumpectomy plus RT provides a greater volume of locoregional therapy and is associated with improved
clinical outcomes in modern population-based studies. Pa- tients will continue to need multidisciplinary evaluations with providers familiar with these issues to help make optimal care decisions.
References
1. Early Breast Cancer Trialists’ Collaborative Group. Effects of radio-
therapy and surgery in early breast cancer e An overview of the
randomized trials. N Engl J Med 1995;333:1444-1456.
2. Lagendijk M, van Maaren MC, Saadatmand S, et al. Breast conserving
therapy and mastectomy revisited: Breast cancer-specific survival and
the influence of prognostic factors in 129,692 patients. Int J Cancer
2018;142:165-175.
3. Agarwal S, Pappas L, Neumayer L, et al. Effect of breast conservation
therapy vs mastectomy on disease-specific survival for early-stage
breast cancer. JAMA Surg 2014;149:267-274.
4. Chen K, Liu J, Zhu L, et al. Comparative effectiveness study of breast-
conserving surgery and mastectomy in the general population: A
NCDB analysis. Oncotarget 2015;6:40127-40140.
5. Hwang ES, Lichtensztajn DY, Gomez SL, et al. Survival after lump-
ectomy and mastectomy for early stage invasive breast cancer. Cancer
2013;119:1402-1411.
6. Fisher S, Gao H, Yasui Y, et al. Survival in stage I-III breast cancer
patients by surgical treatment in a publicly funded health care system.
Ann Oncol 2015;26:1161-1169.
7. Hartmann-Johnsen OJ, Karesen R, Schlichting E, et al. Survival is
better after breast conserving therapy than mastectomy for early stage
breast cancer: A registry-based follow-up study of Norwegian women
primary operated between 1998 and 2008. Ann Surg Oncol 2015;22:
3836-3845.
8. van Marren MC, de Munck L, de Bock GH, et al. 10 year survival after
breast-conserving surgery plus radiotherapy compared with mastec-
tomy in early breast cancer in The Netherlands: A population-based
study. Lancet Oncol 2016;17:1158-1170.
9. van Laar C, van der Sangen MJ, Poortmans PM, et al. Local recur-
rence following breast-conserving treatment in women aged 40 years
or younger: Trends in risk and the impact on prognosis in a
population-based cohort of 1143 patients. Eur J Cancer 2013;49:
3093-3101.
10. Arvold ND, Taghian AG, Niemierko A, et al. Age, breast cancer
subtype approximation, and local recurrence after breast-conserving
therapy. J Clin Oncol 2011;29:3885-3891.
11. Smith BL, Tang R, Rai U, et al. Oncologic safety of nipple-sparing
mastectomy in women with breast cancer. J Am Coll Surg 2017;225:
361-365.
12. Tang R, Coopey SB, Merrill AL, et al. Positive nipple margins in
nipple-sparing mastectomies: Rates, management, and oncologic
safety. J Am Coll Surg 2016;222:1149-1155.
13. Robertson SA, Rusby JE, Cutress RI. Determinants of optimal mas-
tectomy skin flap thickness. Br J Surg 2014;101:899-911.
14. Giannotti DG, Hanna SA, Cerri GG, et al. Analysis of skin flap
thickness and residual breast tissue after mastectomy. Int J Radiat
Oncol Biol Phys 2018;102:82-91.
15. Poortmans PM, Collette S, Kirkove C, et al. Internal mammary and
medical supraclavicular irradiation in breast cancer. N Engl J Med
2015;373:317-327.
16. Whelan TJ, Olivottto IA, Parulekar WR, et al. Regional nodal irra-
diation in early-stage breast cancer. N Engl J Med 2015;373:307-316.
References
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