Pathologic response and residual tumor cellularity after neo-adjuvant chemotherapy predict prognosis in breast cancer patients

by Damiano Gentile, Andrea Sagona, Camilla De Carlo, Bethania Fernandes, Erika Barbieri, Simone Di Maria Grimaldi, Flavia Jacobs, Giulia Vatteroni, Lorenzo Scardina, Ersilia Biondi, Valeriano Vinci, Rubina Manuela Trimboli, Daniela Bernardi, Corrado Tinterri 

The Breast: Published: March 27, 2023

Introduction

Residual tumor cellularity (RTC) and pathologic complete response (pCR) after neo-adjuvant chemotherapy (NAC) are prognostic factors associated with improved outcomes in breast cancer (BC). However, the majority of patients achieve partial pathologic response (pPR) and no clear correlation between RTC patterns and outcomes was described. Our aims were to define predictive factors for pCR and compare different outcomes of patients with pCR or pPR and with different RTC patterns.

Materials and methods

Baseline and post-NAC demographics, clinicopathological characteristics, post-operative data, survival and recurrence status were recorded from our institutional database. A multivariable analysis was performed using a logistic regression model to identify independent predictors of pCR. Disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) analyses were performed using the Kaplan-Meier method.

Results

Overall, of the 495 patients analyzed, 148 (29.9%) achieved pCR, 347 (70.1%) had pPR, and the median RTC was 40%. Multivariable analysis identified 3 independent factors predictive of pCR: tumor stage before NAC (cT1-2 84.5% versus cT3-4 15.5%), BC sub-type (HER2-positive 54.7% versus triple-negative 29.8% versus luminal-like 15.5%), and vascular invasion (absence 98.0% versus presence 2.0%). We found statistically significant longer DFS, DDFS, and OS in patients with pCR and with RTC <40%; no difference was observed in terms of OS between RTC <40% and RTC ≥40% groups.

Conclusions

Tumor stage before NAC, BC sub-type, and vascular invasion are significant and independent factors associated with pCR. Patients with pCR and with RTC <40% have longer DFS, DDFS, and OS compared with patients with pPR.

 

 

 

Breast and axillary surgery after neoadjuvant systemic treatment – A review of clinical routine recommendations and the latest clinical research

by André Pfob, Joerg Heil 

The Breast: Published:January 22, 2022

Breast and axillary surgery after neoadjuvant systemic treatment for women with breast cancer has undergone multiple paradigm changes within the past years. In this review, we provide a state-of-the-art overview of breast and axillary surgery after neoadjuvant systemic treatment from both, a clinical routine perspective and a clinical research perspective. For axillary disease, axillary lymph node dissection, sentinel lymph node biopsy, or targeted axillary dissection are nowadays recommended depending on the lymph node status before and after neoadjuvant systemic treatment. For the primary tumor in the breast, breast conserving surgery remains the standard of care. The clinical management of exceptional responders to neoadjuvant systemic treatment is a pressing knowledge gap due to the increasing number of patients who achieve a pathologic complete response to neoadjuvant systemic treatment and for whom surgery may have no therapeutic benefit. Current clinical research evaluates whether less invasive procedures can exclude residual cancer after neoadjuvant systemic treatment as reliably as surgery to possibly omit surgery for those patients in the future.

 

Accelerating progress in early triple-negative breast cancer: A viewpoint on antibody-drug conjugates, back from St Gallen breast cancer conference 2021

 

by Dario Trapani, Giuseppe Curigliano 

 

The Breast: Published: December 13, 2021

 

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast tumors, associated with dismal prognosis. Innovative treatments have expanded the therapeutic options for selected patients with advanced disease (mTNBC). Inter alia, the new class of molecules of antibody-drug conjugates (ADCs) has rapidly positioned in the setting of mTNBC, providing significant benefits in pretreated patients. With the advent of ADCs, progresses have been marked in targeting TNBC. Tackling this ‘un-targetable’ tumor type has been the real enterprise of the last years, overcoming the original sin of classification of TNBC in a default ‘non-positive’ category, ultimately grouping together a spectrum of heterogeneous diseases. As such, ADCs have opened an ‘identity crisis’ for TNBC treatments. These molecules are composed of a backbone of monoclonal antibody (MAb), exploiting the best role they are engineered for: recognize antigens. But ADCs are linked to cytotoxic payloads, resulting in tailored delivery of highly active agents, with the intent to spare non-targeted tissues. At the end, they interpret essentially a new pharmacological delivery model to treat tumors

The implementation of ADCs has first modernized the view on MAb clinical utilization: not really only to switch-off hyperactive tumorigenic signaling; ADCs can exert anti-neoplastic activities in disregard of the biologic functions of their pharmacological receptors: antigens are linked, payloads are released, cancer cells are killed via internalized chemotherapies. Such a change in perspective implies that: (i) ADCs can exploit activity across multiple tumor types – delivering agnostically, based on antigen expressions; (ii) ADCs offer an attractive perspective for treatment personalization, based on the multiple targetable antigens that can be identified in a single patient - a possible declination of the theranostic paradigm. Agnosticity and theranosticity, however, will be reached only with an optimal trade-off between antibody specificity – to avoid off-target effects and non-specific activity related to the release of the payload in the bloodstream – and patient tolerance of the cumulative toxicities. Pursuing precision in this context will require understanding better how these new ADCs tailor the targets; perhaps, most importantly, there must be better knowledge on what is the minimal amount of membrane antigen to be expressed, to determine ADCs efficacy, and if traditional techniques like immuno-histochemistry are sensitive enough for this purpose.