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3 pages, 188 KiB

Open AccessEditorial

Diagnostics and Therapeutics in Early Stage Breast Cancer Receiving Neoadjuvant Systemic Therapy

by Paolo Belli, Simone Palma and Melania Costantini

Cancers 2023, 15(19), 4874; https://doi.org/10.3390/cancers15194874 - 07 Oct 2023

Viewed by 690

Abstract

Breast cancer (BC) remains a major challenge for oncology today, impacting the lives of countless individuals worldwide [...] Full article

(This article belongs to the Special Issue Diagnostics and Therapeutics in Early Stage Breast Cancer Receiving Neoadjuvant Systemic Therapy)

Research

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13 pages, 3000 KiB

Open AccessArticle

Selective Axillary Dissection after Neoadjuvant Chemotherapy in Patients with Lymph-Node-Positive Breast Cancer (CLYP Study): The Radio-Guided Occult Lesion Localization Technique for Biopsy-Proven Metastatic Lymph Nodes

by Rossella Rella, Marco Conti, Enida Bufi, Charlotte Marguerite Lucille Trombadori, Alba Di Leone, Daniela Terribile, Riccardo Masetti, Luca Zagaria, Antonino Mulè, Francesca Morciano, Gianluca Franceschini and Paolo Belli

Cancers 2023, 15(7), 2046; https://doi.org/10.3390/cancers15072046 - 29 Mar 2023

Cited by 2 | Viewed by 1503

Abstract

(1) Background: To help to refine the accuracy of sentinel lymph node biopsy (SLNB) in breast cancer (BC) patients with biopsy-proven nodal disease prior to neoadjuvant chemotherapy (NACT), a method of marking the biopsy-proven positive LN at diagnosis to enable its removal during [...] Read more.

(1) Background: To help to refine the accuracy of sentinel lymph node biopsy (SLNB) in breast cancer (BC) patients with biopsy-proven nodal disease prior to neoadjuvant chemotherapy (NACT), a method of marking the biopsy-proven positive LN at diagnosis to enable its removal during surgery was proposed. The aim of this study was to evaluate the accuracy of the Radio-Guided Occult Lesion Localization (ROLL) technique of biopsy-proven metastatic LN in nodal staging after NACT among node-positive BC patients. (2) Methods: Patients with invasive BC and biopsy-proven axillary metastases receiving NACT were enrolled. A clip marker was placed on the sampled LN (clipped lymph node, CLN) before NACT. Before surgery, the ROLL procedure (radioactive tracer injection into CLN under ultrasound guidance) was performed, and the CLN was surgically resected. The correspondence between the CLNs and SLNs was evaluated. The pathologic findings of the CLNs and SLN(s) were compared with remaining axillary nodes at ALND to determine false negative rates (FNRs). (3) Results: Seventy-two patients were analyzed. Surgery successfully identified the CLN in 70/72 procedures (97.2%). For 60/72 patients who underwent ALND, the FNRs dropped from 19.35% for SLNB to 3.13% for CLN biopsy. (4) Conclusions: The ROLL procedure got CLNs is accurate in axillary nodal staging after NACT in node-positive BC patients at diagnosis. Full article

(This article belongs to the Special Issue Diagnostics and Therapeutics in Early Stage Breast Cancer Receiving Neoadjuvant Systemic Therapy)

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15 pages, 2532 KiB

Open AccessArticle

Assessment of Response to Neoadjuvant Systemic Treatment in Triple-Negative Breast Cancer Using Functional Tumor Volumes from Longitudinal Dynamic Contrast-Enhanced MRI

by Bikash Panthi, Beatriz E. Adrada, Rosalind P. Candelaria, Mary S. Guirguis, Clinton Yam, Medine Boge, Huiqin Chen, Kelly K. Hunt, Lei Huo, Ken-Pin Hwang, Anil Korkut, Deanna L. Lane, Huong C. Le-Petross, Jessica W. T. Leung, Jennifer K. Litton, Rania M. Mohamed, Benjamin C. Musall, Sanaz Pashapoor, Miral M. Patel, Frances Perez, Jong Bum Son, Alastair Thompson, Vicente Valero, Peng Wei, Jason White, Zhan Xu, Lawrence Pinsky, Debu Tripathy, Wei Yang, Jingfei Ma and Gaiane M. Rauch Show full author list Hide full author list

Cancers 2023, 15(4), 1025; https://doi.org/10.3390/cancers15041025 - 06 Feb 2023

Cited by 7 | Viewed by 1946

Abstract

Early assessment of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) is critical for patient care in order to avoid the unnecessary toxicity of an ineffective treatment. We assessed functional tumor volumes (FTVs) from dynamic contrast-enhanced (DCE) MRI after 2 cycles [...] Read more.

Early assessment of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) is critical for patient care in order to avoid the unnecessary toxicity of an ineffective treatment. We assessed functional tumor volumes (FTVs) from dynamic contrast-enhanced (DCE) MRI after 2 cycles (C2) and 4 cycles (C4) of NAST as predictors of response in TNBC. A group of 100 patients with stage I-III TNBC who underwent DCE MRI at baseline, C2, and C4 were included in this study. Tumors were segmented on DCE images of 1 min and 2.5 min post-injection. FTVs were measured using the optimized percentage enhancement (PE) and signal enhancement ratio (SER) thresholds. The Mann–Whitney test was used to compare the performance of the FTVs at C2 and C4. Of the 100 patients, 49 (49%) had a pathologic complete response (pCR) and 51 (51%) had a non-pCR. The maximum area under the receiving operating characteristic curve (AUC) for predicting the treatment response was 0.84 (p < 0.001) for FTV at C4 followed by FTV at C2 (AUC = 0.82, p < 0.001). The FTV measured at baseline was not able to discriminate pCR from non-pCR. FTVs measured on DCE MRI at C2, as well as at C4, of NAST can potentially predict pCR and non-pCR in TNBC patients. Full article

(This article belongs to the Special Issue Diagnostics and Therapeutics in Early Stage Breast Cancer Receiving Neoadjuvant Systemic Therapy)

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20 pages, 2400 KiB

Open AccessArticle

Multimodal Prediction of Five-Year Breast Cancer Recurrence in Women Who Receive Neoadjuvant Chemotherapy

by Simona Rabinovici-Cohen, Xosé M. Fernández, Beatriz Grandal Rejo, Efrat Hexter, Oliver Hijano Cubelos, Juha Pajula, Harri Pölönen, Fabien Reyal and Michal Rosen-Zvi

Cancers 2022, 14(16), 3848; https://doi.org/10.3390/cancers14163848 - 09 Aug 2022

Cited by 8 | Viewed by 2975

Abstract

In current clinical practice, it is difficult to predict whether a patient receiving neoadjuvant chemotherapy (NAC) for breast cancer is likely to encounter recurrence after treatment and have the cancer recur locally in the breast or in other areas of the body. We [...] Read more.

In current clinical practice, it is difficult to predict whether a patient receiving neoadjuvant chemotherapy (NAC) for breast cancer is likely to encounter recurrence after treatment and have the cancer recur locally in the breast or in other areas of the body. We explore the use of clinical history, immunohistochemical markers, and multiparametric magnetic resonance imaging (DCE, ADC, Dixon) to predict the risk of post-treatment recurrence within five years. We performed a retrospective study on a cohort of 1738 patients from Institut Curie and analyzed the data using classical machine learning, image processing, and deep learning. Our results demonstrate the ability to predict recurrence prior to NAC treatment initiation using each modality alone, and the possible improvement achieved by combining the modalities. When evaluated on holdout data, the multimodal model achieved an AUC of 0.75 (CI: 0.70, 0.80) and 0.57 specificity at 0.90 sensitivity. We then stratified the data based on known prognostic biomarkers. We found that our models can provide accurate recurrence predictions (AUC > 0.89) for specific groups of women under 50 years old with poor prognoses. A version of our method won second place at the BMMR2 Challenge, with a very small margin from being first, and was a standout from the other challenge entries. Full article

(This article belongs to the Special Issue Diagnostics and Therapeutics in Early Stage Breast Cancer Receiving Neoadjuvant Systemic Therapy)

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16 pages, 3299 KiB

Open AccessArticle

Tumor-Infiltrating Lymphocytes (TILs) in Early Breast Cancer Patients: High CD3⁺, CD8⁺, and Immunoscore Are Associated with a Pathological Complete Response

by Bernardo Leon Rapoport, Simon Nayler, Bernhard Mlecnik, Teresa Smit, Liezl Heyman, Isabelle Bouquet, Marine Martel, Jérôme Galon, Carol-Ann Benn and Ronald Anderson

Cancers 2022, 14(10), 2525; https://doi.org/10.3390/cancers14102525 - 20 May 2022

Cited by 9 | Viewed by 2518

Abstract

Background: Tumor-infiltrating lymphocytes are associated with a better prognosis in early triple-negative breast cancer (TNBC). These cells can be enumerated in situ by the “Immunoscore Clinical Research” (ISCR). The original Immunoscore^® is a prognostic tool that categorizes the densities of CD3⁺ [...] Read more.

Background: Tumor-infiltrating lymphocytes are associated with a better prognosis in early triple-negative breast cancer (TNBC). These cells can be enumerated in situ by the “Immunoscore Clinical Research” (ISCR). The original Immunoscore^® is a prognostic tool that categorizes the densities of CD3⁺ and CD8⁺ cells in both the invasive margin (IM) and center of the tumor (CT) in localized colon cancer, yielding a five-tiered classification (0–4). We evaluated the prognostic potential of ISCR and pathological complete response (pCR) following neoadjuvant chemotherapy (NACT). Methods: The cohort included 53 TNBC, 32 luminal BC, and 18 HER2-positive BC patients undergoing NACT. Pre-treatment tumor biopsies were immune-stained for CD3⁺ and CD8⁺ T-cell markers. Quantitative analysis of these cells in different tumor locations was performed using computer-assisted image analysis. Results: The pCR rate was 44%. Univariate analysis showed that primary tumor size, estrogen-receptor negative, progesterone-receptor negative, luminal vs. HER2-positive vs. TNBC, high Ki-67, high densities (cells/mm²) of CD3 CT, CD8⁺ CT, CD3⁺ IM, and CD8⁺ IM cells were associated with a high pCR. ISCR was associated with pCR following NACT. A multivariate model consisting of ISCR and the significant variables from the univariate analysis showed a significant trend for ISCR; however, the low sample size did not provide enough power for the model to be included in this study. Conclusions: These results revealed a significant prognostic role for the spatial distributions of the CD3⁺, and CD8⁺ lymphocytes, as well as the ISCR in relation to pCR following NACT. Full article

(This article belongs to the Special Issue Diagnostics and Therapeutics in Early Stage Breast Cancer Receiving Neoadjuvant Systemic Therapy)

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Review

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29 pages, 1058 KiB

Open AccessReview

Appraisal of Systemic Treatment Strategies in Early HER2-Positive Breast Cancer—A Literature Review

by Danilo Giffoni de Mello Morais Mata, Rania Chehade, Malek B. Hannouf, Jacques Raphael, Phillip Blanchette, Abdullah Al-Humiqani and Monali Ray

Cancers 2023, 15(17), 4336; https://doi.org/10.3390/cancers15174336 - 30 Aug 2023

Cited by 1 | Viewed by 1319

Abstract

Background: The overexpression of the human epidermal growth factor receptor 2 (HER2+) accounts for 15–20% of all breast cancer phenotypes. Even after the completion of the standard combination of chemotherapy and trastuzumab, relapse events occur in approximately 15% of cases. The neoadjuvant approach [...] Read more.

Background: The overexpression of the human epidermal growth factor receptor 2 (HER2+) accounts for 15–20% of all breast cancer phenotypes. Even after the completion of the standard combination of chemotherapy and trastuzumab, relapse events occur in approximately 15% of cases. The neoadjuvant approach has multiple benefits that include the potential to downgrade staging and convert previously unresectable tumors to operable tumors. In addition, achieving a pathologic complete response (pCR) following preoperative systemic treatment is prognostic of enhanced survival outcomes. Thus, optimal evaluation among the suitable strategies is crucial in deciding which patients should be selected for the neoadjuvant approach. Methods: A literature search was conducted in the Embase, Medline, and Cochrane electronic libraries. Conclusion: The evaluation of tumor and LN staging and, hence, stratifying BC recurrence risk are decisive factors in guiding clinicians to optimize treatment decisions between the neoadjuvant versus adjuvant approaches. For each individual case, it is important to consider the most likely postsurgical outcome, since, if the patient does not obtain pCR following neoadjuvant treatment, they are eligible for adjuvant T-DM1 in the case of residual disease. This review of HER2-positive female BC outlines suitable neoadjuvant and adjuvant systemic treatment strategies for guiding clinical decision making around the selection of an appropriate therapy. Full article

(This article belongs to the Special Issue Diagnostics and Therapeutics in Early Stage Breast Cancer Receiving Neoadjuvant Systemic Therapy)

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21 pages, 3562 KiB

Open AccessReview

Image-Guided Localization Techniques for Metastatic Axillary Lymph Nodes in Breast Cancer; What Radiologists Should Know

by Valerio Di Paola, Giorgio Mazzotta, Marco Conti, Simone Palma, Federico Orsini, Laura Mola, Francesca Ferrara, Valentina Longo, Enida Bufi, Anna D’Angelo, Camilla Panico, Paola Clauser, Paolo Belli and Riccardo Manfredi

Cancers 2023, 15(7), 2130; https://doi.org/10.3390/cancers15072130 - 03 Apr 2023

Cited by 4 | Viewed by 3227

Abstract

Targeted axillary dissection (TAD) is an axillary staging technique after NACT that involves the removal of biopsy-proven metastatic lymph nodes in addition to sentinel lymph node biopsy (SLNB). This technique avoids the morbidity of traditional axillary lymph node dissection and has shown a [...] Read more.

Targeted axillary dissection (TAD) is an axillary staging technique after NACT that involves the removal of biopsy-proven metastatic lymph nodes in addition to sentinel lymph node biopsy (SLNB). This technique avoids the morbidity of traditional axillary lymph node dissection and has shown a lower false-negative rate than SLNB alone. Therefore, marking positive axillary lymph nodes before NACT is critical in order to locate and remove them in the subsequent surgery. Current localization methods include clip placement with intraoperative ultrasound, carbon-suspension liquids, localization wires, radioactive tracer-based localizers, magnetic seeds, radar reflectors, and radiofrequency identification devices. The aim of this paper is to illustrate the management of axillary lymph nodes based on current guidelines and explain the features of axillary lymph node markers, with relative advantages and disadvantages. Full article

(This article belongs to the Special Issue Diagnostics and Therapeutics in Early Stage Breast Cancer Receiving Neoadjuvant Systemic Therapy)

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18 pages, 6681 KiB

Open AccessReview

Surgical Planning after Neoadjuvant Treatment in Breast Cancer: A Multimodality Imaging-Based Approach Focused on MRI

by Marco Conti, Francesca Morciano, Enida Bufi, Anna D’Angelo, Camilla Panico, Valerio Di Paola, Elisabetta Gori, Gianluca Russo, Giovanni Cimino, Simone Palma, Paolo Belli and Riccardo Manfredi

Cancers 2023, 15(5), 1439; https://doi.org/10.3390/cancers15051439 - 24 Feb 2023

Cited by 4 | Viewed by 2911

Abstract

Neoadjuvant chemotherapy (NACT) today represents a cornerstone in the treatment of locally advanced breast cancer and highly chemo-sensitive tumors at early stages, increasing the possibilities of performing more conservative treatments and improving long term outcomes. Imaging has a fundamental role in the staging [...] Read more.

Neoadjuvant chemotherapy (NACT) today represents a cornerstone in the treatment of locally advanced breast cancer and highly chemo-sensitive tumors at early stages, increasing the possibilities of performing more conservative treatments and improving long term outcomes. Imaging has a fundamental role in the staging and prediction of the response to NACT, thus aiding surgical planning and avoiding overtreatment. In this review, we first examine and compare the role of conventional and advanced imaging techniques in preoperative T Staging after NACT and in the evaluation of lymph node involvement. In the second part, we analyze the different surgical approaches, discussing the role of axillary surgery, as well as the possibility of non-operative management after-NACT, which has been the subject of recent trials. Finally, we focus on emerging techniques that will change the diagnostic assessment of breast cancer in the near future. Full article

(This article belongs to the Special Issue Diagnostics and Therapeutics in Early Stage Breast Cancer Receiving Neoadjuvant Systemic Therapy)

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16 pages, 995 KiB

Open AccessReview

Staging Breast Cancer with MRI, the T. A Key Role in the Neoadjuvant Setting

by Camilla Panico, Francesca Ferrara, Ramona Woitek, Anna D’Angelo, Valerio Di Paola, Enida Bufi, Marco Conti, Simone Palma, Stefano Lo Cicero, Giovanni Cimino, Paolo Belli and Riccardo Manfredi

Cancers 2022, 14(23), 5786; https://doi.org/10.3390/cancers14235786 - 24 Nov 2022

Cited by 11 | Viewed by 4255

Abstract

Breast cancer (BC) is the most common cancer among women worldwide. Neoadjuvant chemotherapy (NACT) indications have expanded from inoperable locally advanced to early-stage breast cancer. Achieving a pathological complete response (pCR) has been proven to be an excellent prognostic marker leading to better [...] Read more.

Breast cancer (BC) is the most common cancer among women worldwide. Neoadjuvant chemotherapy (NACT) indications have expanded from inoperable locally advanced to early-stage breast cancer. Achieving a pathological complete response (pCR) has been proven to be an excellent prognostic marker leading to better disease-free survival (DFS) and overall survival (OS). Although diagnostic accuracy of MRI has been shown repeatedly to be superior to conventional methods in assessing the extent of breast disease there are still controversies regarding the indication of MRI in this setting. We intended to review the complex literature concerning the tumor size in staging, response and surgical planning in patients with early breast cancer receiving NACT, in order to clarify the role of MRI. Morphological and functional MRI techniques are making headway in the assessment of the tumor size in the staging, residual tumor assessment and prediction of response. Radiomics and radiogenomics MRI applications in the setting of the prediction of response to NACT in breast cancer are continuously increasing. Tailored therapy strategies allow considerations of treatment de-escalation in excellent responders and avoiding or at least postponing breast surgery in selected patients. Full article

(This article belongs to the Special Issue Diagnostics and Therapeutics in Early Stage Breast Cancer Receiving Neoadjuvant Systemic Therapy)

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15 pages, 3364 KiB

Open AccessReview

Beyond N Staging in Breast Cancer: Importance of MRI and Ultrasound-based Imaging

by Valerio Di Paola, Giorgio Mazzotta, Vincenza Pignatelli, Enida Bufi, Anna D’Angelo, Marco Conti, Camilla Panico, Vincenzo Fiorentino, Francesco Pierconti, Fleur Kilburn-Toppin, Paolo Belli and Riccardo Manfredi

Cancers 2022, 14(17), 4270; https://doi.org/10.3390/cancers14174270 - 31 Aug 2022

Cited by 6 | Viewed by 2911

Abstract

The correct N-staging in breast cancer is crucial to tailor treatment and stratify the prognosis. N-staging is based on the number and the localization of suspicious regional nodes on physical examination and/or imaging. Since clinical examination of the axillary cavity is associated with [...] Read more.

The correct N-staging in breast cancer is crucial to tailor treatment and stratify the prognosis. N-staging is based on the number and the localization of suspicious regional nodes on physical examination and/or imaging. Since clinical examination of the axillary cavity is associated with a high false negative rate, imaging modalities play a central role. In the presence of a T1 or T2 tumor and 0–2 suspicious nodes, on imaging at the axillary level I or II, a patient should undergo sentinel lymph node biopsy (SLNB), whereas in the presence of three or more suspicious nodes at the axillary level I or II confirmed by biopsy, they should undergo axillary lymph node dissection (ALND) or neoadjuvant chemotherapy according to a multidisciplinary approach, as well as in the case of internal mammary, supraclavicular, or level III axillary involved lymph nodes. In this scenario, radiological assessment of lymph nodes at the time of diagnosis must be accurate. False positives may preclude a sentinel lymph node in an otherwise eligible woman; in contrast, false negatives may lead to an unnecessary SLNB and the need for a second surgical procedure. In this review, we aim to describe the anatomy of the axilla and breast regional lymph node, and their diagnostic features to discriminate between normal and pathological nodes at Ultrasound (US) and Magnetic Resonance Imaging (MRI). Moreover, the technical aspects, the advantage and limitations of MRI versus US, and the possible future perspectives are also analyzed, through the analysis of the recent literature. Full article

(This article belongs to the Special Issue Diagnostics and Therapeutics in Early Stage Breast Cancer Receiving Neoadjuvant Systemic Therapy)

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20 pages, 387 KiB

Open AccessReview

Updated Neoadjuvant Treatment Landscape for Early Triple Negative Breast Cancer: Immunotherapy, Potential Predictive Biomarkers, and Novel Agents

by Giovanna Garufi, Luisa Carbognin, Francesco Schettini, Elia Seguí, Alba Di Leone, Antonio Franco, Ida Paris, Giovanni Scambia, Giampaolo Tortora and Alessandra Fabi

Cancers 2022, 14(17), 4064; https://doi.org/10.3390/cancers14174064 - 23 Aug 2022

Cited by 11 | Viewed by 2847

Abstract

Triple-negative breast cancer (TNBC) is characterized by the absence of hormone receptor and HER2 expression, and therefore a lack of therapeutic targets. Anthracyclines and taxane-based neoadjuvant chemotherapy have historically been the cornerstone of treatment of early TNBC. However, genomic and transcriptomic analyses have [...] Read more.

Triple-negative breast cancer (TNBC) is characterized by the absence of hormone receptor and HER2 expression, and therefore a lack of therapeutic targets. Anthracyclines and taxane-based neoadjuvant chemotherapy have historically been the cornerstone of treatment of early TNBC. However, genomic and transcriptomic analyses have suggested that TNBCs include various subtypes, characterized by peculiar genomic drivers and potential therapeutic targets. Therefore, several efforts have been made to expand the therapeutic landscape of early TNBC, leading to the introduction of platinum and immunomodulatory agents into the neoadjuvant setting. This review provides a comprehensive overview of the currently available evidence regarding platinum agents and immune-checkpoint-inhibitors for the neoadjuvant treatment of TNBC, as well as the novel target therapies that are currently being evaluated in this setting. Taking into account the economic issues and the side effects of the expanding therapeutic options, we focus on the potential efficacy biomarkers of the emerging therapies, in order to select the best therapeutic strategy for each specific patient. Full article

(This article belongs to the Special Issue Diagnostics and Therapeutics in Early Stage Breast Cancer Receiving Neoadjuvant Systemic Therapy)

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