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Breast Diseases; De-escalating Treatment: Current Status and Future Directions

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 34302

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Prof. Dr. Thaer Khoury

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Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA
Interests: anatomic pathology; clinical pathology

Special Issue Information

Dear Colleagues,

In recent years, attention has been directed to more personalized medicine in managing and treating breast lesions. A new concept has been introduced, “less is more”, meaning less treatment is better in some instances. This issue will focus on the areas in breast diseases that may benefit from fewer interventions. There are ongoing clinical trials examining active surveillance in managing low-risk DCIS. The majority of high-risk lesions such as lobular neoplasia, radial scars, papilloma, mucocele-like lesions, flat epithelial atypia, and fibroepithelial lesions with cellular stroma have low risks of progressing to more serious disease. Therefore, attention should be directed to the conservative management of such lesions. With the introduction of molecular assays for luminal-type breast cancers, many patients are spared unnecessary chemotherapies. The axillary region can be spared from unnecessary lymph node dissection based on the Z11 clinical trial. Some patients can avoid requiring a mastectomy by the separate excision of detected lesions. They are also ongoing trials to de-escalate surgical interventions in patients who achieve complete clinical responses after neoadjuvant chemotherapy. Extensive research has shown that tumor-infiltrating lymphocytes (TILs) play major roles in the response to chemotherapy in triple-negative breast cancer. Therefore, there is a call for de-escalating the chemotherapeutic regimen for patients with tumors high in TILs.

Prof. Dr. Thaer Khoury
Guest Editor

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Keywords

breast cancer
de-escalating
active surveillance
high-risk lesions
luminal type
triple-negative
conservative surgery
axillary lymph nodes

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Published Papers (11 papers)

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Editorial

Jump to: Research, Review

4 pages, 203 KiB

Open AccessEditorial

The Evolving Approach to Breast Cancer: Moving toward De-Escalating Treatment and Personalized Medicine

by Thaer Khoury

Cancers 2023, 15(13), 3502; https://doi.org/10.3390/cancers15133502 - 5 Jul 2023

Cited by 2 | Viewed by 1038

Abstract

In recent years, more attention has been directed to personalized medicine in the management and treatment of breast cancer (BC) [...] Full article

(This article belongs to the Special Issue Breast Diseases; De-escalating Treatment: Current Status and Future Directions)

Research

Jump to: Editorial, Review

10 pages, 1458 KiB

Open AccessArticle

External Beam Accelerated Partial Breast Irradiation in Early Breast Cancer and the Risk for Radiogenic Pneumonitis

by Oliver J. Ott, Wilhelm Stillkrieg, Ulrike Lambrecht, Tim-Oliver Sauer, Claudia Schweizer, Allison Lamrani, Vratislav Strnad, Carolin C. Hack, Matthias W. Beckmann, Michael Uder, Rainer Fietkau and Luitpold Distel

Cancers 2022, 14(14), 3520; https://doi.org/10.3390/cancers14143520 - 20 Jul 2022

Cited by 5 | Viewed by 2135

Abstract

In order to evaluate the risk for radiation-associated symptomatic pneumonitis in a prospective external beam accelerated partial breast irradiation (APBI) trial, between 2011 and 2021, 170 patients with early stage breast cancer were enclosed in the trial. Patients were eligible for study participation if they had a histologically confirmed breast cancer or an exclusive ductal carcinoma in situ (DCIS), a tumor size ≤3 cm, free safety margins ≥2 mm, no involved axillary lymph nodes, tumor bed clips, and were ≥50 years old. Patients received APBI with 38 Gy with 10 fractions in 10 consecutive working days. The trial was registered at the German Clinical Trials Registry, DRKS-ID: DRKS00004417. Median follow-up was 56 (1–129) months. Ipsilateral lung MLD, V20, and V30 were 4.3 ± 1.4 Gy, 3.0 ± 2.0%, and 1.0 ± 1.0%, respectively. Radiogenic pneumonitis grade 2 appeared in 1/170 (0.6%) patients two months after radiotherapy. Ipsilateral MLD, V20, and V30 were 6.1 Gy, 7, and 3% in this patient. Additionally, individual radiosensitivity was increased in this specific patient. Compared to WBI, APBI leads to lower lung doses. Using APBI, the risk of symptomatic radiogenic pneumonitis is very low and may be limited, with an ipsilateral V20 < 3% to very exceptional cases associated with innate risk factors with an increased radiation susceptibility. Full article

(This article belongs to the Special Issue Breast Diseases; De-escalating Treatment: Current Status and Future Directions)

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12 pages, 1021 KiB

Open AccessArticle

A Retrospective Study Assessing the Outcomes of Immediate Prepectoral and Subpectoral Implant and Mesh-Based Breast Reconstruction

by Thomas Wow, Agnieszka Kolacinska-Wow, Mateusz Wichtowski, Katarzyna Boguszewska-Byczkiewicz, Zuzanna Nowicka, Katarzyna Ploszka, Karolina Pieszko and Dawid Murawa

Cancers 2022, 14(13), 3188; https://doi.org/10.3390/cancers14133188 - 29 Jun 2022

Cited by 6 | Viewed by 2635

Abstract

(1) Introduction: In response to patient concerns about breast cancer recurrence, increased use of breast magnetic resonance imaging and genetic testing, and advancements in breast reconstruction techniques, mastectomy rates have been observed to rise over the last decade. The aim of the study is to compare the outcomes of prepectoral and subpectoral implants and long-term, dual-stage resorbable mesh-based breast reconstructions in mutation carriers (prophylactic surgery) and breast cancer patients. (2) Patients and methods: This retrospective, two-center study included 170 consecutive patients after 232 procedures: Prepectoral surgery was performed in 156 cases and subpectoral was performed in 76. (3) Results: Preoperative chemotherapy was associated with more frequent minor late complications (p < 0.001), but not major ones (p = 0.101), while postoperative chemotherapy was related to more frequent serious (p = 0.005) postoperative complications. Postoperative radiotherapy was associated with a higher rate of minor complications (31.03%) than no-radiotherapy (12.21%; p < 0.001). Multivariate logistic regression found complications to be significantly associated with an expander (OR = 4.43), skin-reducing mastectomy (OR = 9.97), therapeutic mastectomy vs. risk-reducing mastectomy (OR = 4.08), and postoperative chemotherapy (OR = 12.89). Patients in whom prepectoral surgeries were performed demonstrated significantly shorter median hospitalization time (p < 0.001) and lower minor complication rates (5.77% vs. 26.32% p < 0.001), but similar major late complication rates (p = 0.915). (4) Conclusions: Implant-based breast reconstruction with the use of long-term, dual-stage resorbable, synthetic mesh is a safe and effective method of breast restoration, associated with low morbidity and good cosmesis. Nevertheless, prospective, multicenter, and long-term outcome data studies are needed to further evaluate the benefits of such treatments. Full article

(This article belongs to the Special Issue Breast Diseases; De-escalating Treatment: Current Status and Future Directions)

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17 pages, 7466 KiB

Open AccessArticle

Level II Oncoplastic Surgery as an Alternative Option to Mastectomy with Immediate Breast Reconstruction in the Neoadjuvant Setting: A Multidisciplinary Single Center Experience

by Alba Di Leone, Antonio Franco, Daniela Andreina Terribile, Stefano Magno, Alessandra Fabi, Alejandro Martin Sanchez, Sabatino D’Archi, Lorenzo Scardina, Maria Natale, Elena Jane Mason, Federica Murando, Fabio Marazzi, Armando Orlandi, Ida Paris, Giuseppe Visconti, Antonella Palazzo, Valeria Masiello, Liliana Barone Adesi, Marzia Salgarello, Riccardo Masetti and Gianluca Franceschini Show full author list Hide full author list

Cancers 2022, 14(5), 1275; https://doi.org/10.3390/cancers14051275 - 1 Mar 2022

Cited by 9 | Viewed by 4104

Abstract

Oncoplastic surgery level II techniques (OPSII) are used in patients with operable breast cancer. There is no evidence regarding their safety and efficacy after neoadjuvant chemotherapy (NAC). The aim of this study was to compare the oncological and aesthetic outcomes of this technique compared with those observed in mastectomy with immediate breast reconstruction (MIBR), in post-NAC patients undergoing surgery between January 2016 and March 2021. Local disease-free survival (L-DFS), regional disease-free survival (R-DFS), distant disease-free survival (D-DFS), and overall survival (OS) were compared; the aesthetic results and quality of life (QoL) were evaluated using BREAST-Q. A total of 297 patients were included, 87 of whom underwent OPSII and 210 of whom underwent MIBR. After a median follow-up of 39.5 months, local recurrence had occurred in 3 patients in the OPSII group (3.4%), and in 13 patients in the MIBR group (6.1%) (p = 0.408). The three-year L-DFS rates were 95.1% for OPSII and 96.2% for MIBR (p = 0.286). The three-year R-DFS rates were 100% and 96.4%, respectively (p = 0.559). The three-year D-DFS rate were 90.7% and 89.7% (p = 0.849). The three-year OS rates were 95.7% and 95% (p = 0.394). BREAST-Q highlighted significant advantages in physical well-being for OPSII. No difference was shown for satisfaction with breasts (p = 0.656) or psychosocial well-being (p = 0.444). OPSII is safe and effective after NAC. It allows oncological and aesthetic outcomes with a high QoL, and is a safe alternative for locally advanced tumors which are partial responders to NAC. Full article

(This article belongs to the Special Issue Breast Diseases; De-escalating Treatment: Current Status and Future Directions)

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12 pages, 707 KiB

Open AccessArticle

Type of Recurrence, Cause of Death and Second Neoplasms among 737 Patients with Ductal Carcinoma In Situ of the Breast—15-Year Follow-Up

by Anna Niwińska and Michał Kunkiel

Cancers 2022, 14(3), 669; https://doi.org/10.3390/cancers14030669 - 28 Jan 2022

Cited by 4 | Viewed by 2391

Abstract

Aim: To assess the outcomes of 737 consecutive patients with DCIS, with particular attention to the type of recurrences, other malignancies and causes of deaths. Material and Methods: A retrospective analysis of 737 consecutive DCIS patients treated in one institution in the years 1996–2011 was carried out. The cumulative recurrence risk, DFS, OS depending on the method of treatment (mastectomy, breast-conserving treatment (BCT), breast-conserving surgery (BCS)) and cause of death were assessed. Results: Sixty-six recurrences (42% DCIS, 58% invasive) were reported: 61 in the breast and 5 outside the breast. The cumulative recurrence risk after a 15-year observation after mastectomy, BCT and BCS was 3.2%, 19.5% and 31.2%, respectively (p < 0.001). The 15-year DFS after mastectomy, BCT and BCS was 72%, 65% and 48%, respectively (p < 0.001). The 15-year OS after mastectomy, BCT and BCS was 75%, 83% and 70%, respectively (p = 0.329). Deaths due to DCIS progression were reported in four (0.5%) of the overall patients and in 10.5% of patients with invasive recurrences. The majority of deaths were linked to the age of the patients or other diseases, including other neoplasms, but not DCIS. Conclusions: The highest number of recurrences was reported in patients after BCS, despite the fact that it was the lowest-risk group. In total, 79% of local recurrences were true recurrences and 58% were invasive recurrences. Local recurrences were effectively treated without an influence on the OS. The percentage of deaths due to DCIS was low and mainly concerned patients with locoregional and distant failure. Full article

(This article belongs to the Special Issue Breast Diseases; De-escalating Treatment: Current Status and Future Directions)

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12 pages, 2213 KiB

Open AccessArticle

Long-Term Outcomes of Breast Cancer Patients Who Underwent Selective Neck Dissection for Metachronous Isolated Supraclavicular Nodal Metastasis

by Shin-Cheh Chen, Shih-Che Shen, Chi-Chang Yu, Ting-Shuo Huang, Yung-Feng Lo, Hsien-Kun Chang, Yung-Chang Lin, Wen-Ling Kuo, Hsiu-Pei Tsai, Hsu-Huan Chou, Li-Yu Lee and Yi-Ting Huang

Cancers 2022, 14(1), 164; https://doi.org/10.3390/cancers14010164 - 29 Dec 2021

Cited by 4 | Viewed by 2194

Abstract

We retrospectively enrolled 139 patients who developed metachronous isolated supraclavicular lymph node metastasis (miSLNM) from 8129 consecutive patients who underwent primary surgery between 1990 and 2008 at a single medical center. The median age was 47 years. The median follow-up time from date of primary tumor surgery was 73.1 months, and the median time to the date of neck relapse was 43.9 months in this study. Sixty-one (43.9%) patients underwent selective neck dissection (SND). The 5-year distant metastasis-free survival (DMFS), post-recurrence survival, and overall survival (OS) rates in the SND group were 31.1%, 40.3%, and 68.9%, respectively, whereas those of the no-SND group were 9.7%, 32.9%, and 57.7%, respectively (p = 0.001). No SND and time interval from primary tumor surgery to neck relapse ≤24 months were the only significant risk factors in the multivariate analysis of DMFS (hazard ratio (HR), 1.77; 95% confidence interval (CI), 1.23–2.56; p = 0.002 and HR, 1.76, 95% CI, 1.23–2.52; p = 0.002, respectively) and OS (HR, 1.77; 95% CI, 1.22–2.55; p = 0.003 and HR, 3.54, 95% CI, 2.44–5.16; p < 0.0001, respectively). Multimodal therapy, including neck dissection, significantly improved the DMFS and OS of miSLNM. Survival improvement after miSLNM control by intensive surgical treatment suggests that miSLNM is not distant metastasis. Full article

(This article belongs to the Special Issue Breast Diseases; De-escalating Treatment: Current Status and Future Directions)

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18 pages, 1249 KiB

Open AccessArticle

Predictors of Sentinel Lymph Node Metastasis in Postoperatively Upgraded Invasive Breast Carcinoma Patients

by Chi-Chang Yu, Yun-Chung Cheung, Chuen Hsueh and Shin-Cheh Chen

Cancers 2021, 13(16), 4099; https://doi.org/10.3390/cancers13164099 - 14 Aug 2021

Cited by 5 | Viewed by 2618

Abstract

Sentinel lymph node (SLN) biopsy (SLNB) usually need not be simultaneously performed with breast-conserving surgery (BCS) for patients diagnosed with ductal carcinoma in situ (DCIS) by preoperative core needle biopsy (CNB), but must be performed once there is invasive carcinoma (IC) found postoperatively. This study aimed to investigate the factors contributing to SLN metastasis in underestimated IC patients with an initial diagnosis of DCIS by CNB. We retrospectively reviewed 1240 consecutive cases of DCIS by image-guided CNB from January 2010 to December 2017 and identified 316 underestimated IC cases with SLNB. Data on clinical characteristics, radiologic features, and final pathological findings were examined. Twenty-three patients (7.3%) had SLN metastasis. Multivariate analysis indicated that an IC tumor size > 0.5 cm (odds ratio: 3.11, p = 0.033) and the presence of lymphovascular invasion (odds ratio: 32.85, p < 0.0001) were independent risk predictors of SLN metastasis. In the absence of any predictors, the incidence of positive SLNs was very low (2.6%) in the total population and extremely low (1.3%) in the BCS subgroup. Therefore, omitting SLNB may be an acceptable option for patients who initially underwent BCS without risk predictors on final pathological assessment. Further prospective studies are necessary before clinical application. Full article

(This article belongs to the Special Issue Breast Diseases; De-escalating Treatment: Current Status and Future Directions)

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14 pages, 629 KiB

Open AccessArticle

Preferences of Treatment Strategies among Women with Low-Risk DCIS and Oncologists

by Danalyn Byng, Valesca P. Retèl, Ellen G. Engelhardt, Catharina G. M. Groothuis-Oudshoorn, Janine A. van Til, Renée S. J. M. Schmitz, Frederieke van Duijnhoven, Jelle Wesseling, Eveline Bleiker, Wim H. van Harten and on behalf of the Grand Challenge Precision Consortium

Cancers 2021, 13(16), 3962; https://doi.org/10.3390/cancers13163962 - 6 Aug 2021

Cited by 10 | Viewed by 3149

Abstract

As ongoing trials study the safety of an active surveillance strategy for low-risk ductal carcinoma in situ (DCIS), there is a need to explain why particular choices regarding treatment strategies are made by eligible women as well as their oncologists, what factors enter the decision process, and how much each factor affects their choice. To measure preferences for treatment and surveillance strategies, women with newly-diagnosed, primary low-risk DCIS enrolled in the Dutch CONTROL DCIS Registration and LORD trial, and oncologists participating in the Dutch Health Professionals Study were invited to complete a discrete choice experiment (DCE). The relative importance of treatment strategy-related attributes (locoregional intervention, 10-year risk of ipsilateral invasive breast cancer (iIBC), and follow-up interval) were discerned using conditional logit models. A total of n = 172 patients and n = 30 oncologists completed the DCE. Patient respondents had very strong preferences for an active surveillance strategy with no surgery, irrespective of the 10-year risk of iIBC. Extensiveness of the locoregional treatment was consistently shown to be an important factor for patients and oncologists in deciding upon treatment strategies. Risk of iIBC was least important to patients and most important to oncologists. There was a stronger inclination toward a twice-yearly follow-up for both groups compared to annual follow-up. Full article

(This article belongs to the Special Issue Breast Diseases; De-escalating Treatment: Current Status and Future Directions)

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Review

Jump to: Editorial, Research

13 pages, 299 KiB

Open AccessReview

De-Escalating the Management of In Situ and Invasive Breast Cancer

by Fernando A. Angarita, Robert Brumer, Matthew Castelo, Nestor F. Esnaola, Stephen B. Edge and Kazuaki Takabe

Cancers 2022, 14(19), 4545; https://doi.org/10.3390/cancers14194545 - 20 Sep 2022

Cited by 11 | Viewed by 2528

Abstract

It is necessary to identify appropriate areas of de-escalation in breast cancer treatment to minimize morbidity and maximize patients’ quality of life. Less radical treatment modalities, or even no treatment, have been reconsidered if they offer the same oncologic outcomes as standard therapies. Identifying which patients benefit from de-escalation requires particular care, as standard therapies will continue to offer adequate cancer outcomes. We provide an overview of the literature on the de-escalation of treatment of ductal carcinoma in situ (DCIS), local treatment of breast cancer, and surgery after neoadjuvant systemic therapy. De-escalation of breast cancer treatment is a key area of investigation that will continue to remain a priority. Improvements in understanding the natural history and biology of breast cancer, imaging modalities, and adjuvant treatments will expand this even further. Future efforts will continue to challenge us to consider the true role of various treatment modalities. Full article

(This article belongs to the Special Issue Breast Diseases; De-escalating Treatment: Current Status and Future Directions)

22 pages, 315 KiB

Open AccessReview

Systemic Therapy De-Escalation in Early-Stage Triple-Negative Breast Cancer: Dawn of a New Era?

by Ravi Kumar Gupta, Arya Mariam Roy, Ashish Gupta, Kazuaki Takabe, Ajay Dhakal, Mateusz Opyrchal, Pawel Kalinski and Shipra Gandhi

Cancers 2022, 14(8), 1856; https://doi.org/10.3390/cancers14081856 - 7 Apr 2022

Cited by 17 | Viewed by 5131

Abstract

Early-stage triple negative breast cancer (TNBC) has been traditionally treated with surgery, radiation, and chemotherapy. The current standard of care systemic treatment of early-stage II and III TNBC involves the use of anthracycline-cyclophosphamide and carboplatin-paclitaxel with pembrolizumab in the neoadjuvant setting followed by adjuvant pembrolizumab per KEYNOTE-522. It is increasingly clear that not all patients with early-stage TNBC need this intensive treatment, thus paving the way for exploring opportunities for regimen de-escalation in selected subgroups. For T1a tumors (≤5 mm), chemotherapy is not used, and for tumors 6–10 mm (T1b) in size with negative lymph nodes, retrospective studies have failed to show a significant benefit with chemotherapy. In low-risk patients, anthracycline-free chemotherapy may be as effective as conventional therapy, as shown in some studies where replacing anthracyclines with carboplatin has shown non-inferior results for pathological complete response (pCR), which may form the backbone of future combination therapies. Recent advances in our understanding of TNBC heterogeneity, mutations, and surrogate markers of response such as pCR have enabled the development of multiple treatment options in the (neo)adjuvant setting in order to de-escalate treatment. These de-escalation studies based on tumor mutational status, such as using Poly ADP-ribose polymerase inhibitors (PARPi) in patients with BRCA mutations, and new immunotherapies such as PD1 blockade, have shown a promising impact on pCR. In addition, the investigational use of (bio)markers, such as high levels of tumor-infiltrating lymphocytes (TILs), low levels of tumor-associated macrophages (TAMs), and complete remission on imaging, also look promising. In this review, we cover the current standard of care systemic treatment of early TNBC and review the opportunities for treatment de-escalation based on clinical risk factors, biomarkers, mutational status, and molecular subtype. Full article

(This article belongs to the Special Issue Breast Diseases; De-escalating Treatment: Current Status and Future Directions)

20 pages, 2700 KiB

Open AccessReview

Preneoplastic Low-Risk Mammary Ductal Lesions (Atypical Ductal Hyperplasia and Ductal Carcinoma In Situ Spectrum): Current Status and Future Directions

by Thaer Khoury

Cancers 2022, 14(3), 507; https://doi.org/10.3390/cancers14030507 - 20 Jan 2022

Cited by 5 | Viewed by 5099

Abstract

Intraepithelial mammary ductal neoplasia is a spectrum of disease that varies from atypical ductal hyperplasia (ADH), low-grade (LG), intermediate-grade (IG), to high-grade (HG) ductal carcinoma in situ (DCIS). While ADH has the lowest prognostic significance, HG-DCIS carries the highest risk. Due to widely used screening mammography, the number of intraepithelial mammary ductal neoplastic lesions has increased. The consequence of this practice is the increase in the number of patients who are overdiagnosed and, therefore, overtreated. The active surveillance (AS) trials are initiated to separate lesions that require active treatment from those that can be safely monitored and only be treated when they develop a change in the clinical/radiologic characteristics. At the same time, the natural history of these lesions can be evaluated. This review aims to evaluate ADH/DCIS as a spectrum of intraductal neoplastic disease (risk and histomorphology); examine the controversies of distinguishing ADH vs. DCIS and the grading of DCIS; review the upgrading for both ADH and DCIS with emphasis on the variation of methods of detection and the definitions of upgrading; and evaluate the impact of all these variables on the AS trials. Full article

(This article belongs to the Special Issue Breast Diseases; De-escalating Treatment: Current Status and Future Directions)

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