|Year : 2021 | Volume
| Issue : 3 | Page : 96-99
Radiation therapy as an adjuvant treatment after breast-conserving surgery in ductal carcinoma In situ of the breast
Marwen Benna, Raouia Ben Amor, Zeineb Naimi, Meriem Bohli, Lotfi Kochbati
Department of Radiation Oncology, Abderrahmen Mami Hospital, 2080, Ariana; University of Tunis El Manar, Faculty of Medicine of Tunis, 1007, Tunisia
|Date of Submission||10-Aug-2021|
|Date of Acceptance||13-Aug-2021|
|Date of Web Publication||03-Sep-2021|
Dr. Raouia Ben Amor
Department of Radiation Oncology, Abderrahmen Mami Hospital, 2080, Ariana; University of Tunis El Manar, Faculty of Medicine of Tunis, 1007
Source of Support: None, Conflict of Interest: None
Ductal carcinoma in situ (DCIS) of the breast is a nonmalignant tumor of the breast with a rising incidence due to systematic mammographic screening. Actual consensus on conservative therapy is based on lumpectomy followed by adjuvant radiation therapy to the whole breast. This approach has been established after multiple large clinical trials and confirmed with subsequent meta-analyses. However, there are still debates on the benefit of adjuvant radiation therapy in a largely undefined “low-risk population.” This review tries to discuss actual data on this matter and discuss the benefits and risks of radiation therapy after lumpectomy in DCIS.
Keywords: Breast cancer, breast-conserving surgery, ductal carcinoma in situ, radiotherapy
|How to cite this article:|
Benna M, Amor RB, Naimi Z, Bohli M, Kochbati L. Radiation therapy as an adjuvant treatment after breast-conserving surgery in ductal carcinoma In situ of the breast. J Radiat Cancer Res 2021;12:96-9
|How to cite this URL:|
Benna M, Amor RB, Naimi Z, Bohli M, Kochbati L. Radiation therapy as an adjuvant treatment after breast-conserving surgery in ductal carcinoma In situ of the breast. J Radiat Cancer Res [serial online] 2021 [cited 2022 May 17];12:96-9. Available from: https://www.journalrcr.org/text.asp?2021/12/3/96/325567
| Introduction|| |
Ductal carcinoma in situ of the breast (DCIS) is more and more common with an increase of incidence over the years in the US and Europe by five times for 25 years., This is might be explained by the widespread use of mammographic screening worldwide which would be responsible for an increase of previously undetected DCIS. DCIS is not directly linked to an increase of mortality in patients. However, invasive recurrence may occur which is associated with breast-cancer mortality.
Adjuvant radiation therapy after lumpectomy was established as a standard of care after The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17 clinical trial and confirmed with further prospective trials.,, Nevertheless, doubts arose on the benefit of radiation therapy through the years through lackluster analysis of limited series of patients and unproven fear of side effects.
We sought to retrace the history behind the adoption of adjuvant radiation therapy as a standard of care after lumpectomy in DCIS while considering novel approaches and future perspectives.
| Adjuvant Radiation Therapy to the Whole Mammary Gland|| |
Breast-conservative treatment of DCIS was established in the 80s as the combination of in Sano excision followed by radiation therapy., The benefit of adjuvant radiation therapy was explained by the frequency of muticentric DCIS foci and the residual DCIS after lumpectomy.
The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17 clinical trial was designed to evaluate the benefits of adjuvant radiation therapy after lumpectomy in DCIS and lobular carcinoma in situ. Eight hundred and eighteen women were randomized to receive lumpectomy with or without adjuvant radiation therapy to the whole breast. The prescribed dose was 50 Gy to the whole breast delivered in a conventional technique, 5 sessions of 2 Gy/week. Nine percent of patients received an additional boost to the tumor site.
After a mean follow-up of 43 months (11–86), the event-free survival rate in patients treated with radiation therapy was significantly higher (84.4% vs. 73.8%, P = 0.001). In the ipsilateral breast, radiation therapy significantly reduced invasive breast cancer from 2.6% to 0.6%. In the contralateral breast, 18 events were detected (8 in the lumpectomy alone group versus 10 in the adjuvant radiation therapy group), 11 of them were invasive breast cancer. Second cancer rates were similar in both arms (5 in the lumpectomy group versus 8 in the adjuvant radiation therapy group). There were five deaths in the lumpectomy arm and two in the radiation therapy arm.
A later report confirmed these results after 8 years of follow-up. Nevertheless, overall survival (OS) rates were similar in both arms 94% for women treated by lumpectomy alone and 95% for women who received radiation therapy following lumpectomy (relative risk = 1.07; 95% confidence interval, 0.82–1.39; P = 0.84). This study concluded that adjuvant radiation therapy was to be indicated in all patients with DCIS since there was no method to identify patients with a significant ipsilateral invasive relapse probability.
Similar clinical trials such as The European Organization for Research and Treatment of Cancer-10853 and the SweDCIS Clinical Trials demonstrated similar results with a better local failure rate in the adjuvant radiation therapy arm (18%–20%) versus lumpectomy alone (31%–32%) after a respective 15.8 and 17 years of median follow-up., The Early Breast Cancer Trialists' Collaborative Group performed a meta-analysis of 5 clinical trials randomizing lumpectomy alone versus lumpectomy followed by radiation therapy. Three thousand nine hundred and twenty-five patients were analyzed, some of which received endocrine therapy and some received a boost to the tumor bed. After a median follow-up of 8.9 years, radiation therapy was demonstrated to significantly reduce local failure with no impact on mortality. The lack of impact on mortality might be explained by the rarity of events, the efficiency of salvage therapy and the indirect impact of local relapse on mortality.,
Following these results, adjuvant radiation therapy to the whole breast was considered a standard of care after lumpectomy.,, However, questions arose in the following years to determine the population that would not benefit from this treatment.,, The rationale behind this was to spare patients from radiation therapy side effects if it was not needed. This population would be selected based on previously demonstrated prognostic factors.
Younger age (40–50) was associated with more frequent local recurrences in randomized clinical trials and retrospective studies.,,,, Coincidentally, the effect of radiation therapy on local relapses was less important in younger women., This fact prompted some institutions into more radical approaches in younger with more frequent radical mastectomies or radiation therapy boost to the tumor bed.
Defining sufficient margins in the management of DCIS is still a challenge up to this day. Throughout the history of treating DCIS, different consensuses have been adopted ranging from no ink on tumor up to 10 mm of margins., In the NASBP B-17 and SweDCIS clinical trials, no clear definition of sufficient margin was given., This is one of the main critics of these trials and some authors suggested that the benefit of radiation therapy was tributary to insufficient margins., While it has been demonstrated that wider margins were associated with better local control, the benefit of radiation therapy is significant with all margins although lesser in margins above 5 mm.
Higher tumor size was reported to be associated with more local relapses., Various definitions were used in different studies ranging from 15 to 20 mm., The problem with measuring these tumors is especially in low-grade DCIS that might look like normal breast cells with even discontinuous growth patterns that do not fall under the definition of multifocal locii.,
High nuclear grade is associated with lesser local control and has been considered an independent prognostic factor.,, With tumor size and margins, nuclear grade determines the Van Nuys Prognostic Index which is a useful and reproducible prognostic score in DCIS.
Based on these prognostic factors, the Radiation Therapy Oncology Group 9804 clinical trial tested de-escalation in patients with “low-risk DCIS.” The main critics that can be addressed to these trials are the lack of identified subgroups with no benefits of radiation therapy in previous studies and the absence of reasons to omit radiation therapy from a toxicity standpoint. From the start, this clinical trial was designed to fail since it could not define a population that would need a change of standard and could not justify why this population would need it in the first place.
The “low-risk DCIS” group of patients was defined by a tumor size under 25 mm, age over 26, and margins over 3 mm. The clinical trial was closed at 636 inclusions instead of the 1790 planned ones for not meeting accrual targets. Even with the limited number, lumpectomy alone was significantly associated with more local failures: Cumulative rates of LF in the ipsilateral breast at 5 and 7 years were 0.4% and 0.9% in the RT arm versus 3.5% and 6.7% in the observation arm, respectively (P < 0.001). Moreover, local failures were at 42.1% invasive. These results were irrespective of the use of endocrine therapy.
These results were confirmed by other clinical trials such as the Korean Radiation Oncology Group 11-04 and 16-02 studies, the Eastern Cooperative Oncology Group-Alliance for Clinical Trials in Oncology E5194 study, and the Dana–Farber Cancer Institute Trial.
Despite the shortcomings of de-escalation, exploring subgroups of patients with low-risk disease is still ongoing based on clinical and pathologic features previously discussed in the DUCHESS clinical trial (NCT02766881), immunohistochemistry findings combined with clinical and pathologic features in the ROMANCE clinical trial (NCT03878342), or even, anecdotal use of multigene assays.,
| Conclusion|| |
The standard of care in patients with DCIS seeking conservative treatment is lumpectomy followed by adjuvant radiation therapy to the whole breast. All clinical trials up to this date point to the same results irrespective of tumor and patient characteristics. Future perspective should address the need of tumor bed boost which is debatable and is being explored with on-going clinical trials such as the BONBIS clinical trial (NCT00907868).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Glover JA, Bannon FJ, Hughes CM, Cantwell MM, Comber H, Gavin A, et al.
Increased diagnosis and detection rates of carcinoma in situ
of the breast. Breast Cancer Res Treat 2012;133:779-84.
Lynge E, Ponti A, James T, Májek O, von Euler-Chelpin M, Anttila A, et al.
Variation in detection of ductal carcinoma in situ
(DCIS) during screening mammography A survey with in the international cancer screening network (ICSN). Eur J Cancer 2014;50. [doi: 10.1016/j.ejca. 2013.08.013].
van Steenbergen LN, Voogd AC, Roukema JA, Louwman WJ, Duijm LE, Coebergh JW, et al.
Screening caused rising incidence rates of ductal carcinoma in situ
of the breast. Breast Cancer Res Treat 2009;115:181-3.
Cutuli B, Bernier J, Poortmans P. Radiotherapy in DCIS, an underestimated benefit? Radiother Oncol 2014;112:1-8.
Fisher B, Costantino J, Redmond C, Fisher E, Margolese R, Dimitrov N, et al.
Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer. N Engl J Med 1993;328:1581-6.
Fisher B, Dignam J, Wolmark N, Mamounas E, Costantino J, Poller W, et al.
Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: Findings from national surgical adjuvant breast and bowel project B-17. J Clin Oncol 1998;16:441-52.1.
Donker M, Litière S, Werutsky G, Julien JP, Fentiman IS, Agresti R, et al.
Breast-conserving treatment with or without radiotherapy in ductal carcinoma in situ
: 15-year recurrence rates and outcome after a recurrence, from the EORTC 10853 randomized phase III trial. J Clin Oncol 2013;31:4054-9.
Kim T, Park HK, Lee KH, Kim KI, Lee KC, Ahn JS, et al.
Is radiotherapy necessary for intermediate risk ductal carcinoma in situ
after breast conserving surgery? Springerplus 2014;3:405.
Silverstein MJ. Ductal carcinoma in situ
of the breast: 11 reasons to consider treatment with excision alone. Womens Health (Lond) 2008;4:565-77.
Schnitt SJ, Silen W, Sadowsky NL, Connolly JL, Harris JR. Ductal carcinoma in situ
(intraductal carcinoma) of the breast. N Engl J Med 1988;318:898-903.
Lagios MD. Duct carcinoma in situ
: Pathology and treatment. Surg Clin North Am 1990;70:853-71.
Zafrani B, Fourquet A, Vilcoq JR, Legal M, Calle R. Conservative management of intraductalbreastcarcinomawithtumorectomy and radiation therapy. Cancer 1986;57:1299-301.
Wärnberg F, Garmo H, Emdin S, Hedberg V, Adwall L, Sandelin K, et al.
Effect of radiotherapy after breast-conserving surgery for ductal carcinoma in situ
: 20 years follow-up in the randomized SweDCIS Trial. J Clin Oncol 2014;32:3613-8.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Correa C, McGale P, Taylor C, Wang Y, Clarke M, et al.
Overview of the randomized trials of radiotherapy in ductal carcinoma in situ
of the breast. J Natl Cancer Inst Monogr 2010;2010:162-77.
Recht A. Are the randomized trials of radiation therapy for ductal carcinoma in situ
still relevant? J Clin Oncol 2014;32:3588-90.
Rakovitch E, Nofech-Mozes S, Narod SA, Hanna W, Thiruchelvam D, Saskin R, et al.
Can we select individuals with low risk ductal carcinoma in situ
(DCIS)? A population-based outcomes analysis. Breast Cancer Res Treat 2013;138:581-90.
Skandarajah AR, Bruce Mann G. Selective use of whole breast radiotherapy after breast conserving surgery for invasive breast cancer and DCIS. Surgeon 2013;11:278-85.
Viani GA, Stefano EJ, Afonso SL, De Fendi LI, Soares FV, Leon PG, et al.
Breast-conserving surgery with or without radiotherapy in women with ductal carcinoma in situ
: A meta-analysis of randomized trials. Radiat Oncol 2007;2:28.
Meijnen P, Oldenburg HS, Peterse JL, Bartelink H, Rutgers EJ. Clinical outcome after selective treatment of patients diagnosed with ductal carcinoma in situ
of the breast. Ann Surg Oncol 2008;15:235-43.
MacDonald HR, Silverstein MJ, Mabry H, Moorthy B, Ye W, Epstein MS, et al.
Local control in ductal carcinoma in situ
treated by excision alone: Incremental benefit of larger margins. Am J Surg 2005;190:521-5.
Bijker N, Peterse JL, Duchateau L, Julien JP, Fentiman IS, Duval C, et al.
Riskfactors for recurrence and metastasis after breast-conserving therapy for ductal carcinoma-in-situ
: Analysis of European organization for research and treatment of cancer trial 10853. J Clin Oncol 2001;19:2263-71.
Holmberg L, Garmo H, Granstrand B, Ringberg A, Arnesson LG, Sandelin K, et al.
Absoluteriskreductions for local recurrenceafterpostoperativeradiotherapyaftersectorresection for ductalcarcinoma in situ
of the breast. J Clin Oncol 2008;26:1247-52. [doi: 10.1200/JCO.2007.12.7969].
Shah C, Vicini F, Wazer DE, Arthur D, Patel RR. The American brachytherapy society consensus statement for accelerated partial breast irradiation. Brachytherapy 2013;12:267-77.
Sagara Y, Freedman RA, Vaz-Luis I, Mallory MA, Wong SM, Aydogan F, et al.
Patient prognostic score and associations with survival improvement offered by radiotherapy after breast-conserving surgery for ductal carcinoma in situ
: A population-based longitudinal cohort study. J Clin Oncol 2016;34:1190-6.
Smith GL, Smith BD, Haffty BG. Rationalization and regionalization of treatment for ductal carcinoma in situ
of the breast. Int J Radiat Oncol Biol Phys 2006;65:1397-403.
Solin LJ, Fourquet A, Vicini FA, Haffty B, Taylor M, McCormick B, et al.
Mammographically detected ductal carcinoma in situ
of the breast treated with breast-conserving surgery and definitive breast irradiation: Long-term outcome and prognostic significance of patient age and margin status. Int J Radiat Oncol Biol Phys 2001;50:991-1002.
Morrow M, Brinkmann E. Surgical overview of the treatment of ductal carcinoma in situ
ed. In: Silverstein MJ, Recht A, Lagios M, editors. Ductal Carcinoma in situ
of the Breast. Philadelphia: Lippincott William and Wilkins; 2002. p. 275-86.
Moran MS, Zhao Y, Ma S, Kirova Y, Fourquet A, Chen P, et al.
Association of radiotherapy boost for ductal carcinoma in situ
with local control after whole-breast radiotherapy. JAMA Oncol 2017;3:1060-8.
Sahoo S, Recant WM, Jaskowiak N, Tong L, Heimann R. Defining negative margins in DCIS patients treated with breast conservation therapy: The University of Chicago experience. Breast J 2005;11:242-7.
Silverstein MJ, Lagios MD, Groshen S, Waisman JR, Lewinsky BS, Martino S, et al.
The influence of margin width on local control of ductal carcinoma in situ
of the breast. N Engl J Med 1999;340:1455-61.
Dunne C, Burke JP, Morrow M, Kell MR. Effect of margin status on local recurrence after breast conservation and radiation therapy for ductal carcinoma in situ
. J Clin Oncol 2009;27:1615-20.
Wang SY, Chu H, Shamliyan T, Jalal H, Kuntz KM, Kane RL, et al.
Network meta-analysis of margin threshold for women with ductal carcinoma in situ
. J Natl Cancer Inst 2012;104:507-16.
Cutuli B, Lemanski C, Fourquet A, de Lafontan B, Giard S, Meunier A, et al.
Breast-conserving surgery with or without radiotherapy vs. mastectomy for ductal carcinoma in situ
: French survey experience. Br J Cancer 2009;100:1048-54.
Alvarado R, Lari SA, Roses RE, Smith BD, Yang W, Mittendorf EA, et al.
Biology, treatment, and outcome in very young and older women with DCIS. Ann Surg Oncol 2012;19:3777-84.
Allred DC. Ductal carcinoma in situ
: Terminology, classification, and natural history. J Natl Cancer Inst Monogr 2010;2010:134-8.
Vargas C, Kestin L, Go N, Krauss D, Chen P, Goldstein N, et al.
Factors associated with local recurrence and cause-specific survival in patients with ductal carcinoma in situ
of the breast treated with breast-conserving therapy or mastectomy. Int J Radiat Oncol Biol Phys 2005;63:1514-21.
Sagara Y, Julia W, Golshan M, Toi M. Paradigm shift toward reducing overtreatment of ductal carcinoma in situ
of breast. Front Oncol 2017;7:192.
Cutuli B, Wiezzane N, Palumbo I, Barbieri P, Guenzi M, Huscher A, et al.
Breast-conserving treatment for ductal carcinoma in situ
: Impact of boost and tamoxifen on local recurrences. Cancer Radiother 2016;20:292-8.
Silverstein MJ, Lagios MD, Craig PH, Waisman JR, Lewinsky BS, Colburn WJ, et al
. A prognostic index for ductal carcinoma in situ
of the breast. Cancer 1996;77:2267-74.
McCormick B, Winter K, Hudis C, Kuerer HM, Rakovitch E, Smith BL, et al.
RTOG 9804: A prospective randomized trial for good-risk ductal carcinoma in situ
comparing radiotherapy with observation. J Clin Oncol 2015;33:709-15.
Kim K, Kim JH, Kim YB, Suh CO, Shin KH, Kim JH, et al.
Selective radiation therapy for ductal carcinoma in situ
following breast-conserving surgery according to age and margin width: Korean radiation oncology group 11-04 and 16-02 studies. J Breast Cancer 2017;20:327-32.
Solin LJ, Gray R, Hughes LL, Wood WC, Lowen MA, Badve SS, et al.
Surgical excision without radiation for ductal carcinoma in situ
of the breast: 12-year results from the ECOG-ACRIN E5194 study. J Clin Oncol 2015;33:3938-44.
Lalani N, Rakovitch E. Improving Therapeutic Ratios with the Oncotype DX® Ductal Carcinoma In Situ (DCIS) Score. Cureus. 2017 Apr 21;9(4):e1185. doi: 10.7759/cureus.1185. PMID: 28534000; PMCID: PMC5438234.
Nofech-Mozes S, Hanna W, Rakovitch E. Molecular evaluation of breast ductal carcinoma in situ
with oncotype DX DCIS. Am J Pathol 2019;189:975-80.