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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 12  |  Issue : 3  |  Page : 96-99

Radiation therapy as an adjuvant treatment after breast-conserving surgery in ductal carcinoma In situ of the breast


Department of Radiation Oncology, Abderrahmen Mami Hospital, 2080, Ariana; University of Tunis El Manar, Faculty of Medicine of Tunis, 1007, Tunisia

Date of Submission10-Aug-2021
Date of Acceptance13-Aug-2021
Date of Web Publication03-Sep-2021

Correspondence Address:
Dr. Raouia Ben Amor
Department of Radiation Oncology, Abderrahmen Mami Hospital, 2080, Ariana; University of Tunis El Manar, Faculty of Medicine of Tunis, 1007
Tunisia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrcr.jrcr_24_21

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  Abstract 


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 2021 Dec 5];12:96-9. Available from: https://www.journalrcr.org/text.asp?2021/12/3/96/325567




  Introduction Top


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.[1],[2] This is might be explained by the widespread use of mammographic screening worldwide which would be responsible for an increase of previously undetected DCIS.[3] DCIS is not directly linked to an increase of mortality in patients. However, invasive recurrence may occur which is associated with breast-cancer mortality.[4]

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.[5],[6],[7] Nevertheless, doubts arose on the benefit of radiation therapy through the years through lackluster analysis of limited series of patients[8] and unproven fear of side effects.[9]

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 Top


Breast-conservative treatment of DCIS was established in the 80s as the combination of in Sano excision followed by radiation therapy.[10],[11] The benefit of adjuvant radiation therapy was explained by the frequency of muticentric DCIS foci and the residual DCIS after lumpectomy.[12]

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.[5]

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.[6]

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.[7],[13] 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.[14] 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.[4],[15]

Following these results, adjuvant radiation therapy to the whole breast was considered a standard of care after lumpectomy.[16],[17],[18] However, questions arose in the following years to determine the population that would not benefit from this treatment.[9],[19],[20] 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.

Age

Younger age (40–50) was associated with more frequent local recurrences in randomized clinical trials and retrospective studies.[21],[22],[23],[24],[25] Coincidentally, the effect of radiation therapy on local relapses was less important in younger women.[22],[26] This fact prompted some institutions into more radical approaches in younger with more frequent radical mastectomies[27] or radiation therapy boost to the tumor bed.[28]

Margins

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.[29],[30] In the NASBP B-17 and SweDCIS clinical trials, no clear definition of sufficient margin was given.[5],[13] 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.[30],[31] While it has been demonstrated that wider margins were associated with better local control,[32] the benefit of radiation therapy is significant with all margins although lesser in margins above 5 mm.[33]

Tumor size

Higher tumor size was reported to be associated with more local relapses.[24],[25] Various definitions were used in different studies ranging from 15 to 20 mm.[34],[35] 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.[10],[36]

Nuclear grade

High nuclear grade is associated with lesser local control and has been considered an independent prognostic factor.[37],[38],[39] With tumor size and margins, nuclear grade determines the Van Nuys Prognostic Index which is a useful and reproducible prognostic score in DCIS.[40]

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.[41]

These results were confirmed by other clinical trials such as the Korean Radiation Oncology Group 11-04 and 16-02 studies,[42] the Eastern Cooperative Oncology Group-Alliance for Clinical Trials in Oncology E5194 study,[43] and the Dana–Farber Cancer Institute Trial.[44]

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.[45],[46]


  Conclusion Top


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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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