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Neoadjuvant Therapy for Breast Cancer

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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 (10 January 2023) | Viewed by 30237

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Special Issue Editor

Dr. Luigi Cavanna

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Guest Editor

Oncologia Medica ed Ematologia, USL di Piacenza, Ospedale Guglielmo da Saliceto, 29121 Piacenza, Italy
Interests: cancer patients; metastatic cancer; supportive care; neoadjuvant treatment; adjuvant treatment; immune-checkpoint inhibitors; chemotherapy; COVID-19 and cancer

Special Issue Information

Dear Colleagues,

Neoadjuvant chemotherapy (associated or not with target therapy) has become an important therapeutic choice in the treatment of locally advanced and early-stage breast cancer. The goal of neoadjuvant treatment is not only to reduce the tumor volume, allowing radical surgery, but also to be able to achieve less invasive surgery both on the breast (lumpectomy vs. mastectomy), and axilla (sentinel node biopsy vs. axillary dissection) in case of downstaging. Moreover, neoadjuvant chemotherapy has an important predictive and prognostic role. Indeed, in HER2 positive and triple negative breast cancer, neoadjuvant treatment is able to obtain an early assessment of the efficacy of the drugs and therefore the possibility of modifying the treatment in case of non-response, the choice of an optimal adjuvant therapy in case of residual disease, translational research improvement of novel biological markers unique to individual patients allowing appropriate targeted therapy, and a higher probability of pathological complete response which represents a favorable prognostic factor in terms of DFS.

We are pleased to invite you to write an article for this Special Issue on neoadjuvant chemotherapy for locally advanced and early-stage breast cancer. This Special Issue aims to improve knowledge regarding neoadjuvant therapy for breast cancer.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: breast cancer, neoadjuvant, adjuvant, pathological complete response, biomarkers, chemotherapy, and target therapy.

We look forward to receiving your contributions.

Dr. Luigi Cavanna
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

breast cancer
neoadjuvant
adjuvant
pathological complete response
biomarkers
chemotherapy
target therapy

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Published Papers (9 papers)

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Research

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14 pages, 1000 KiB

Open AccessArticle

The Use of San-Huang-Xie-Xin-Tang Reduces the Mortality Rate among Breast Cancer Patients

by Daniel Winardi, Chieh-Hsin Wu, Jen-Huai Chiang, Yung-Hsiang Chen, Ching-Liang Hsieh, Juan-Cheng Yang and Yang-Chang Wu

Cancers 2023, 15(4), 1213; https://doi.org/10.3390/cancers15041213 - 14 Feb 2023

Cited by 5 | Viewed by 1950

Abstract

Globally, breast cancer is the most common cause of cancer deaths. In Taiwan, it is the most prevalent cancer among females. Since San-Huang-Xie-Xin-Tang (SHXXT) exerts not only an anti-inflammatory but an immunomodulatory effect, it may act as a potent anti-tumor agent. Herein, the study aimed to explore the influence of SHXXT and its constituents on the mortality rate among breast cancer patients in Taiwan regarding the component effect and the dose–relationship effect. By using the Taiwan National Health Insurance (NHI) Research Database (NHIRD), the study analyzed 5387 breast cancer patients taking Chinese herbal medicine (CHM) and 5387 breast cancer patients not using CHM. CHM means SHXXT and its constituents in the study. The Kaplan–Meier method was utilized to determine the mortality probabilities among patients. Whether the CHM influences the mortality rate among patients was estimated by Cox proportional hazard regression analysis. The use of CHM could lower the cancer mortality rate by 59% in breast cancer patients. The protective effect was parallel to the cumulative days of CHM use and the annual average CHM dose. In addition, the mortality rate was lower in patients who used SHXXT compared to those who only used one of its constituents. SHXXT and its constituents were all promising therapeutic weapons against breast cancer. Full article

(This article belongs to the Special Issue Neoadjuvant Therapy for Breast Cancer)

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17 pages, 754 KiB

Open AccessArticle

Factors Associated with Axillary Lymph Node Status in Clinically Node-Negative Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

by Chi-Chang Yu, Yun-Chung Cheung, Shir-Hwa Ueng, Yung-Chang Lin, Wen-Ling Kuo, Shih-Che Shen, Yung-Feng Lo and Shin-Cheh Chen

Cancers 2022, 14(18), 4451; https://doi.org/10.3390/cancers14184451 - 14 Sep 2022

Cited by 3 | Viewed by 1998

Abstract

Adequate axillary lymph node (ALN) staging is critical for patients with invasive breast cancer. However, neoadjuvant chemotherapy (NAC) was associated with a lower risk of ALN metastasis compared with those who underwent primary surgery among clinically node-negative (cN0) patients. This study aimed to investigate the factors associated with ALN status among patients with cN0 breast cancer undergoing NAC. A total of 222 consecutive patients with cN0 breast cancer undergoing NAC between January 2012 and December 2021 were reviewed. Univariate and multivariate analyses were performed to compare factors associated with positive ALN status. Seventeen patients (7.7%) had ALNs metastases. Here, 90 patients (40.5%) achieved pathologic complete response in the breast (breast-pCR), and all had negative ALN status. Lymphovascular invasion (odds ratio: 29.366, p < 0.0001) was an independent risk predictor of ALN metastasis in all study populations. Among patients without breast-pCR, mastectomies were performed more frequently in patients with ALN metastasis (52.9%) than in those without metastasis (20.9%) (p = 0.013). Our findings support the omission of axillary surgery in patients who achieve breast-pCR. Prospective studies are needed to confirm the feasibility of a future two-stage surgical plan for breast-conserving surgery in patients who are likely to achieve breast-pCR during clinical evaluation. Full article

(This article belongs to the Special Issue Neoadjuvant Therapy for Breast Cancer)

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12 pages, 1556 KiB

Open AccessArticle

An Integrative Clinical Model for the Prediction of Pathological Complete Response in Patients with Operable Stage II and Stage III Triple-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy

by Wai-Shan Chung, Shin-Cheh Chen, Tai-Ming Ko, Yung-Chang Lin, Sheng-Hsuan Lin, Yung-Feng Lo, Shu-Chi Tseng and Chi-Chang Yu

Cancers 2022, 14(17), 4170; https://doi.org/10.3390/cancers14174170 - 28 Aug 2022

Cited by 5 | Viewed by 2150

Abstract

Triple-negative breast cancer (TNBC) is treated with neoadjuvant chemotherapy (NAC). The response to NAC, particularly the probability of a complete pathological response (pCR), guides the surgical approach and adjuvant therapy. We developed a prediction model using a nomogram integrating blood tests and pre-treatment ultrasound findings for predicting pCR in patients with stage II or III operable TNBC receiving NAC. Clinical data before and after the first cycle of NAC collected from patients between 2012 and 2019 were analyzed using univariate and multivariate analyses to identify correlations with pCR. The coefficients of the significant parameters were calculated using logistic regression, and a nomogram was developed based on the logistic model to predict the probability of pCR. Eighty-eight patients were included. Five parameters correlated with the probability of pCR, including the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte (PLR) ratio, percentage change in PLR, presence of echogenic halo, and tumor height-to-width ratio. The discrimination performance of the nomogram was indicated by an area under the curve of 87.7%, and internal validation showed that the chi-square value of the Hosmer–Lemeshow test was 7.67 (p = 0.363). Thus, the integrative prediction model using clinical data can predict the probability of pCR in patients with TNBC receiving NAC. Full article

(This article belongs to the Special Issue Neoadjuvant Therapy for Breast Cancer)

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15 pages, 947 KiB

Open AccessArticle

Different Prognostic Values of Tumour and Nodal Response to Neoadjuvant Chemotherapy Depending on Subtypes of Inflammatory Breast Cancer, a 317 Patient-Study

by Maximilien Rogé, Julia Salleron, Youlia Kirova, Marin Guigo, Axel Cailleteau, Christelle Levy, Marianne Leheurteur, Rafik Nebbache, Eleonor Rivin Del Campo, Ioana Lazarescu, Stéphanie Servagi, Maud Aumont, Juliette Thariat and Sébastien Thureau

Cancers 2022, 14(16), 3928; https://doi.org/10.3390/cancers14163928 - 15 Aug 2022

Cited by 6 | Viewed by 1783

Abstract

Inflammatory breast cancer (IBC) is a rare entity with a poor prognosis. We analysed the survival outcomes of patients with nonmetastatic IBC and the prognostic value of tumour or nodal responses to assess their individual prognostic impact across IBC subtypes. This retrospective multicentre study included patients diagnosed with IBC between 2010 and 2017 to account for advances in neoadjuvant systemic therapies and modern radiotherapy at seven oncology centres in France. Three hundred and seventeen patients were included and analysed. After a median follow-up of 52 months, the 5-year DFS was lower for triple-negative (TN) (50.1% vs. 63.6%; p < 0.0001). After multivariate analyses, incomplete nodal response was the only significant prognostic factor in the triple-negative group (HR:6.06). The poor prognosis of TN-IBC was reversed in the case of nodal response after neoadjuvant chemotherapy. Breast response does not appear to be a decisive prognostic factor in patients with TN-IBC compared to lymph node response. Despite improvements in neoadjuvant treatments, IBC remains associated with a poor prognosis. In TN-IBC patients, lack of pathological complete node response was associated with poorer survival than any other group. Treatment intensification strategies are worth investigating. Full article

(This article belongs to the Special Issue Neoadjuvant Therapy for Breast Cancer)

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16 pages, 3871 KiB

Open AccessArticle

The Effect of Intratumoral Interrelation among FOXP3+ Regulatory T Cells on Treatment Response and Survival in Triple-Negative Breast Cancer

by Noriko Goda, Chika Nakashima, Ichiro Nagamine and Sunao Otagaki

Cancers 2022, 14(9), 2138; https://doi.org/10.3390/cancers14092138 - 25 Apr 2022

Cited by 8 | Viewed by 2148

Abstract

Triple-negative breast cancer (TNBC) is characterized by an active immune response. We evaluated intratumoral interrelation between FOXP3+ tumor-infiltrating lymphocytes and other cytokines in TNBC. Network analysis refined cytokines significantly correlate with FOPX3 in TNBC. Information on the treatment response and prognosis of patients, and survival data from the TGCA and METABRIC databases were analyzed according to refined cytokines. Interleukin (IL)-33 was significantly expressed by TNBC cell lines compared to luminal cell lines (log₂ fold change: 5.31, p < 0.001) and IL-33 and TGFB2 showed a strong correlation with FOXP3 in the TNBC cell line. Immunohistochemistry demonstrated that the IL-33 high group was a significant predictor of complete response of neoadjuvant chemotherapy (odds ratio (OR) 4.12, p < 0.05) and favorable survival compared to the IL-33 low group (OR 6.48, p < 0.05) in TNBC. Survival data from TGCA and METABRIC revealed that FOXP3 was a significantly favorable marker in the IL-33 high group compared to the low IL-33 low group (hazard ratio (HR) 2.1, p = 0.02), and the IL-33 high/TGFB2 high subgroup showed significant favorable prognosis in the FOXP3 high group compared to the FOPX3 low group in TNBC (HR 3.5, p = 0.01). IL-33 and TGFB2 were key cytokines of intratumoral interrelation among FOXP3 in TNBC. Full article

(This article belongs to the Special Issue Neoadjuvant Therapy for Breast Cancer)

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10 pages, 525 KiB

Open AccessArticle

Neoadjuvant Pertuzumab Plus Trastuzumab in Combination with Docetaxel and Carboplatin in Patients with HER2-Positive Breast Cancer: Real-World Data from the National Institute of Oncology in Poland

by Agnieszka Irena Jagiełło-Gruszfeld, Magdalena Rosinska, Małgorzata Meluch, Katarzyna Pogoda, Anna Niwinska, Renata Sienkiewicz, Aleksander Grous, Paweł Winter and Zbigniew I. Nowecki

Cancers 2022, 14(5), 1218; https://doi.org/10.3390/cancers14051218 - 26 Feb 2022

Cited by 3 | Viewed by 2908

Abstract

Neoadjuvant systemic therapy has now become the standard in early breast cancer management. Chemotherapy in combination with trastuzumab +/− pertuzumab targeted therapy can improve the rates of pathologic complete response (pCR) in patients with HER2-positive breast cancer. Achieving a pCR is considered a good prognostic factor, in particular, in patients with more aggressive breast cancer subtypes such as TNBC or HER2-positive cancers. Furthermore, most studies demonstrate that chemotherapy in combination with trastuzumab and pertuzumab is well tolerated. The retrospective analysis presented here concentrates on neoadjuvant therapy with the TCbH-P regimen, with a particular emphasis on patients over 60 years of age. We analysed the factors affecting the achievement of pCR and present the adverse effects of the applied therapies, opening discussion about optimizing the therapy of older patients with HER-2 positive breast cancer. Full article

(This article belongs to the Special Issue Neoadjuvant Therapy for Breast Cancer)

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8 pages, 1393 KiB

Open AccessArticle

Racial/Ethnic Differences and Trends in Pathologic Complete Response Following Neoadjuvant Chemotherapy for Breast Cancer

by Sung Jun Ma, Lucas M. Serra, Brian Yu, Mark K. Farrugia, Austin J. Iovoli, Han Yu, Song Yao, Oluwadamilola T. Oladeru and Anurag K. Singh

Cancers 2022, 14(3), 534; https://doi.org/10.3390/cancers14030534 - 21 Jan 2022

Cited by 11 | Viewed by 2020

Abstract

The purpose of this study was to evaluate nationwide trends in pathologic complete response (pCR) and its racial variations for breast cancer. The National Cancer Database was queried for women from 2010 to 2017 with non-metastatic breast cancer who underwent neoadjuvant chemotherapy. The primary endpoints, pCR and overall survival, were evaluated using Cochran-Armitage test, logistic, and Cox regression multivariable analyses. A total of 104,161 women were analyzed. Overall, pCR improved from 2010 to 2017 (15.1% to 27.2%, trend p < 0.001). Compared to non-Hispanic White (NHW) women, Hispanic White (HW) women were more likely to have pCR for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-positive tumors (adjusted odds ratio (aOR) 1.29, 95% confidence interval (CI) 1.08–1.53, p = 0.005). Black women were less likely to have pCR for HR-HER2+ tumors (aOR 0.81, 95% CI 0.73–0.89, p < 0.001) and triple negative (aOR 0.82, 95% CI 0.77–0.87, p < 0.001) tumors, but more likely for HR+HER2- tumors (aOR 1.13, 95% CI 1.03–1.24, p = 0.009). Among patients who achieved pCR, Asian or Pacific Islander (API) women were associated with better survival (adjusted hazards ratio (aHR) 0.52, 95% CI 0.33–0.82, p = 0.005) than NHW women. Despite positive trends in pCR rates, the likelihood of pCR and survival outcomes may be intricately dependent on racial/ethnic groups and tumor receptor subtypes. Full article

(This article belongs to the Special Issue Neoadjuvant Therapy for Breast Cancer)

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Review

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31 pages, 1603 KiB

Open AccessReview

Predictive Biomarkers of Response to Neoadjuvant Chemotherapy in Breast Cancer: Current and Future Perspectives for Precision Medicine

by Françoise Derouane, Cédric van Marcke, Martine Berlière, Amandine Gerday, Latifa Fellah, Isabelle Leconte, Mieke R. Van Bockstal, Christine Galant, Cyril Corbet and Francois P. Duhoux

Cancers 2022, 14(16), 3876; https://doi.org/10.3390/cancers14163876 - 11 Aug 2022

Cited by 31 | Viewed by 9352

Abstract

Pathological complete response (pCR) after neoadjuvant chemotherapy in patients with early breast cancer is correlated with better survival. Meanwhile, an expanding arsenal of post-neoadjuvant treatment strategies have proven beneficial in the absence of pCR, leading to an increased use of neoadjuvant systemic therapy in patients with early breast cancer and the search for predictive biomarkers of response. The better prediction of response to neoadjuvant chemotherapy could enable the escalation or de-escalation of neoadjuvant treatment strategies, with the ultimate goal of improving the clinical management of early breast cancer. Clinico-pathological prognostic factors are currently used to estimate the potential benefit of neoadjuvant systemic treatment but are not accurate enough to allow for personalized response prediction. Other factors have recently been proposed but are not yet implementable in daily clinical practice or remain of limited utility due to the intertumoral heterogeneity of breast cancer. In this review, we describe the current knowledge about predictive factors for response to neoadjuvant chemotherapy in breast cancer patients and highlight the future perspectives that could lead to the better prediction of response, focusing on the current biomarkers used for clinical decision making and the different gene signatures that have recently been proposed for patient stratification and the prediction of response to therapies. We also discuss the intratumoral phenotypic heterogeneity in breast cancers as well as the emerging techniques and relevant pre-clinical models that could integrate this biological factor currently limiting the reliable prediction of response to neoadjuvant systemic therapy. Full article

(This article belongs to the Special Issue Neoadjuvant Therapy for Breast Cancer)

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37 pages, 1217 KiB

Open AccessReview

Modern Immunotherapy in the Treatment of Triple-Negative Breast Cancer

by Jakub Wesolowski, Anna Tankiewicz-Kwedlo and Dariusz Pawlak

Cancers 2022, 14(16), 3860; https://doi.org/10.3390/cancers14163860 - 10 Aug 2022

Cited by 13 | Viewed by 4563

Abstract

Triple-Negative Breast Cancer is a subtype of breast cancer characterized by the lack of expression of estrogen receptors, progesterone receptors, as well as human epidermal growth factor receptor 2. This cancer accounts for 15–20% of all breast cancers and is especially common in patients under 40 years of age, as well as with the occurring BRCA1 mutation. Its poor prognosis is reflected in the statistical life expectancy of 8–15 months after diagnosis of metastatic TNBC. So far, the lack of targeted therapy has narrowed therapeutic possibilities to classic chemotherapy. The idea behind the use of humanized monoclonal antibodies, as inhibitors of immunosuppressive checkpoints used by the tumor to escape from immune system control, is to reduce immunotolerance and direct an intensified anti-tumor immune response. An abundance of recent studies has provided numerous pieces of evidence about the safety and clinical benefits of immunotherapy using humanized monoclonal antibodies in the fight against many types of cancer, including TNBC. In particular, phase three clinical trials, such as the IMpassion 130, the KEYNOTE-355 and the KEYNOTE-522 resulted in the approval of immunotherapeutic agents, such as atezolizumab and pembrolizumab by the US Food and Drug Administration in TNBC therapy. This review aims to present the huge potential of immunotherapy using monoclonal antibodies directed against immunosuppressive checkpoints—such as atezolizumab, avelumab, durvalumab, pembrolizumab, nivolumab, cemiplimab, tremelimumab, ipilimumab—in the fight against difficult to treat TNBCs as monotherapy as well as in more advanced combination strategies. Full article

(This article belongs to the Special Issue Neoadjuvant Therapy for Breast Cancer)

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