Long-term outcomes of women with large DCIS lesions treated with breast-conserving therapy

Rodin, Danielle; Sutradhar, Rinku; Nofech‐Mozes, Sharon; Gu, Sumei; Faught, Neil; Hahn, Ezra; Fong, Cindy; Trebinjac, Sabina; Paszat, Lawrence; Rakovitch, Eileen

doi:10.1007/s10549-021-06488-x

Cited by 8 publications

(4 citation statements)

References 25 publications

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“…Since most low-grade DCIS will not progress, active surveillance and hormone therapy are currently recommended ( 18 – 20 ). However, larger lesions are often treated with more aggressive therapy ( 55 , 56 ). This larger and higher-grade DCIS may be the lesions where i.duc instilling of IT would be most beneficial.…”

Section: Discussionmentioning

confidence: 99%

“…This larger and higher-grade DCIS may be the lesions where i.duc instilling of IT would be most beneficial. We propose that this intervention could be tested and moved forward in a safe fashion in women with larger DCIS lesions who normally undergo mastectomy since they cannot be resected with breast conservation ( 55 , 56 ). This intervention could be tested preoperatively, and postmastectomy, the duct could be marked with India ink to enable detailed histological examination of the entire ductal tree.…”

Section: Discussionmentioning

confidence: 99%

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Intraductal administration of transferrin receptor-targeted immunotoxin clears ductal carcinoma in situ in mouse models of breast cancer—a preclinical study

Wang

Kumar

Ding

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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The human transferrin receptor (TFR) is overexpressed in most breast cancers, including preneoplastic ductal carcinoma in situ (DCIS). HB21(Fv)-PE40 is a single-chain immunotoxin (IT) engineered by fusing the variable region of a monoclonal antibody (HB21) against a TFR with a 40 kDa fragment of Pseudomonas exotoxin (PE). In humans, the administration of other TFR-targeted immunotoxins intrathecally led to inflammation and vascular leakage. We proposed that for treatment of DCIS, intraductal (i.duc) injection of HB21(Fv)-PE40 could avoid systemic toxicity while retaining its potent antitumor effects on visible and occult tumors in the entire ductal tree. Pharmacokinetic studies in mice showed that, in contrast to intravenous injection, IT was undetectable by enzyme-linked immunosorbent assay in blood following i.duc injection of up to 3.0 μg HB21(Fv)-PE40. We demonstrated the antitumor efficacy of HB21(Fv)-PE40 in two mammary-in-duct (MIND) models, MCF7 and SUM225, grown in NOD/SCID/gamma mice. Tumors were undetectable by In Vivo Imaging System (IVIS) imaging in intraductally treated mice within 1 wk of initiation of the regimen (IT once weekly/3 wk, 1.5 μg/teat). MCF7 tumor–bearing mice remained tumor free for up to 60 d of observation with i.duc IT, whereas the HB21 antibody alone or intraperitoneal IT treatment had minimal/no antitumor effects. These and similar findings in the SUM225 MIND model were substantiated by analysis of mammary gland whole mounts, histology, and immunohistochemistry for the proteins Ki67, CD31, CD71 (TFR), and Ku80. This study provides a strong preclinical foundation for conducting feasibility and safety trials in patients with stage 0 breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Intraductal administration of transferrin receptor-targeted immunotoxin clears ductal carcinoma in situ in mouse models of breast cancer—a preclinical study

Wang

Kumar

Ding

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…However, adequate excision of large DCIS using traditional BCS may compromise the final cosmetic result. Moreover, large DCIS is often a disease with distinct pathological features and high-risk lesions showing either high-grade comedonecrosis or microinvasion are more common than in smaller DCIS [ 19 , 20 , 21 ]. This was also evident in our population of study, where 78.6% of patients presented at least one of these characteristics at final histology ( Table 3 ).…”

Section: Discussionmentioning

confidence: 99%

Oncoplastic Breast Surgery versus Conservative Mastectomy in the Management of Large Ductal Carcinoma In Situ (DCIS): Surgical, Oncological, and Patient-Reported Outcomes

Mason

Leone

Franco

et al. 2022

Cancers

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Oncoplastic level II breast-conserving surgery (OPS2) allows for wider excisions than standard breast-conserving surgery, but the literature on this technique in the treatment of DCIS is scarce. This study compares OPS2 to conservative mastectomy (CM) in patients undergoing surgery for large DCIS. The clinical, radiological, surgical, and post-operative data of 147 patients who underwent either CM or OPS2 for large DCIS between 2007 and 2021 were retrospectively reviewed. The surgical, oncological, and patient-reported outcomes (PRO) were analyzed and compared between the two groups. The surgical outcomes were similar, in terms of margin involvement (p = 0.211), complication rate (p = 0.827), and re-excision rate (p = 1). The rate of additional surgery for cosmetic optimization was significantly lower in the OPS2 group: only 1 (1.8%) patient required surgical adjustments versus 24 (26.4%) patients in the CM group (p < 0.001). The mean hospital stay was lower in the OPS2 group (p < 0.001). The oncological outcomes did not differ between the two groups (p = 0.662). The PRO analysis showed better outcomes in the OPS2 group, which achieved statistical significance in the sexual well-being module (p = 0.015). Skin sensitivity loss was also significantly lower in the OPS2 group (p < 0.001). When feasible, OPS2 should be considered in the treatment of large DCIS, as it is safe and shows high levels of patient satisfaction.

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“…Positive margin and non-screening-detected DCIS were reported to be significantly associated with a higher risk of invasive recurrence in DCIS women in a meta-analysis studying the role of predictive LR factors [49]. A recent study analysing 2049 women treated by BCS, of which 1073 were with radiotherapy, after a median follow-up of 14 years, confirmed BCS + radiotherapy as a feasible option for women with large DCIS size (>40 mm), provided that negative margins can be achieved, and the addition of radiotherapy boost to further reduce the risk of recurrence [50]. The oncoplastic approach is essential in this setting as an oncologically safe tool for obtaining optimal aesthetic outcomes after BCS, performed in selected clinical conditions [51].…”

Section: Margins Valuementioning

confidence: 99%

Ductal Carcinoma In Situ (DCIS) and Microinvasive DCIS: Role of Surgery in Early Diagnosis of Breast Cancer

Magnoni,

Bianchi,

Corso

et al. 2023

Healthcare

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Advances in treatments, screening, and awareness have led to continually decreasing breast cancer-related mortality rates in the past decades. This achievement is coupled with early breast cancer diagnosis. Ductal carcinoma in situ (DCIS) and microinvasive breast cancer have increasingly been diagnosed in the context of mammographic screening. Clinical management of DCIS is heterogenous, and the clinical significance of microinvasion in DCIS remains elusive, although microinvasive DCIS (DCIS-Mi) is distinct from “pure” DCIS. Upfront surgery has a fundamental role in the overall treatment of these breast diseases. The growing number of screen-detected DCIS diagnoses with clinicopathological features of low risk for local recurrence (LR) allows more conservative surgical options, followed by personalised adjuvant radiotherapy plans. Furthermore, studies are underway to evaluate the validity of surgery omission in selected low-risk categories. Nevertheless, the management, the priority of axillary surgical staging, and the prognosis of DCIS-Mi remain the subject of debate, demonstrating how the paucity of data still necessitates adequate studies to provide conclusive guidelines. The current scientific scenario for DCIS and DCIS-Mi surgical approach consists of highly controversial and diversified sources, which this narrative review will delineate and clarify.

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Long-term outcomes of women with large DCIS lesions treated with breast-conserving therapy

Cited by 8 publications

References 25 publications

Intraductal administration of transferrin receptor-targeted immunotoxin clears ductal carcinoma in situ in mouse models of breast cancer—a preclinical study

Intraductal administration of transferrin receptor-targeted immunotoxin clears ductal carcinoma in situ in mouse models of breast cancer—a preclinical study

Oncoplastic Breast Surgery versus Conservative Mastectomy in the Management of Large Ductal Carcinoma In Situ (DCIS): Surgical, Oncological, and Patient-Reported Outcomes

Ductal Carcinoma In Situ (DCIS) and Microinvasive DCIS: Role of Surgery in Early Diagnosis of Breast Cancer

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