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Jan 04 / Springer Healthcare

SABCS 2020 In-Depth Report: Triple-negative breast cancer (TNBC)

Description

This in-depth report covers sessions on the pathogenesis, diagnosis and treatment of triple-negative breast cancer at SABCS 2020.

SABCS 2020

San Antonio Breast Cancer Symposium

December 8th – 11th, 2020

In-Depth Report

Welcome to SABCS 2020

 

SABCS 2020 at a glance

In response to the COVID-19 global pandemic, the 43rd SABCS took place on a new virtual congress platform from the 8th to the 11th December 2020. This year’s meeting continued the tradition of bringing together breast cancer researchers and clinicians from around the world, providing a virtual format to present new and late-breaking data on the experimental biology, aetiology, prevention, diagnosis, and therapy of breast cancer, along with premalignant breast disease. SABCS is the premier event for researchers, health professionals, and those with a special interest in breast cancer and this year included more than 40 oral presentations in four general sessions. Also included were commentaries from expert discussants, as well as poster sessions consisting of short audio overviews from the authors. Co-Chair Carlos L. Arteaga, Dallas, USA, opened the meeting and welcomed attendees.

 
 

Triple-negative breast cancer (TNBC)

 

Lisa A. Carey, Chapel Hill, USA, provided an overview of ‘state-of-the-art’ treatment for neoadjuvant/adjuvant TNBC. Dr Carey explained that systemic therapy for TNBC remains limited to chemotherapy, with ongoing focus on the type and timing of chemotherapy, along with optimising locoregional management of the primary tumour. Although TNBC typically has a poor prognosis, there are patient subsets that can achieve excellent clinical outcomes.

Cytoreduction with neoadjuvant chemotherapy can facilitate breast conserving surgery, with around 50% of patients initially considered ineligible subsequently being deemed as eligible following treatment. In addition, a high proportion of patients with node-positive breast cancer can be converted to node-negative status, thus removing the need for axillary dissection, while also reducing the risk of lymphoedema. Available data also suggest that pathologic complete response (pCR) to chemotherapy across all subtypes of breast cancer carries a markedly better prognosis compared with residual disease.

Key improvements in chemotherapy regimens for TNBC

Modern systemic chemotherapy regimens, where anthracyclines are the basis and neoadjuvant therapy is standard, are effective in TNBC but it has the highest risk of relapse of all subtypes of breast cancer. Additional biomarkers may allow more tailored treatment in the future.

Systemic therapy of TNBC in 2020: key points

“While TNBC carries the worst prognosis of the clinical subtypes, the overall prognosis has improved with modern treatment approaches.”

Lisa A. Carey, Chapel Hill, USA

Jennifer K. Litton, Houston, USA, provided a brief overview of new treatments for metastatic TNBC, given that a number of new therapies have been recently approved. Dr Litton explained that exciting new strategies have emerged further to the increasing recognition that TNBCs are a very heterogeneous group of tumours. Traditionally, treatment for locally advanced or metastatic breast cancer has solely revolved around sequential chemotherapies, either alone or in combination. For immunotherapy, nab-paclitaxel and atezolizumab can be used in patients with locally advanced or metastatic triple negative breast cancer with PD-L1 positive tumour-infiltrating immune cells.

nab-paclitaxel+atezolizumab versus placebo in TNBC

Of note, further analyses of data from Impassion130 showed no therapeutic benefit in PD-L1 negative patients. Sacituzumab govitecan is a novel antibody-drug-conjugate (ADC) targeting trophoblast-antigen-2 (Trop-2), a cell surface glycoprotein highly expressed in many epithelial tumours, to deliver SN-38, the active metabolite of irinotecan. Of note, Trop-2 has been estimated to be expressed in up to 90% of TNBC, thus making it an attractive target for an ADC. The phase III ASCENT study in patients with metastatic TNBC who had received at least two prior lines of therapy in the metastatic setting demonstrated an improvement in median PFS from 1.7 to 5.6 months (HR 0.41; 95% CI: 0.32, 0.52) for patients who received sacituzumab versus physician’s choice of therapy. In addition, there was an improvement in median OS of 6.7 to 12.1 months (HR 0.48; 95% CI: 0.38, 0.59).

Two PARP inhibitors – olaparib and talazoparib – now have FDA approval for use in patients with metastatic breast cancer and a germline BRCA pathogenic variant. Of note, while both agents have demonstrated improvements in PFS, along with significant improvement in quality-of-life measures, neither the OlympiAD (olaparib) nor EMBRACA (talazoparib) studies reported significant improvement in OS.

“New therapies and combinations with checkpoint inhibitors and other novel immunomodulatory agents are forthcoming.”

Jennifer K. Litton, Houston, USA

Javier Cortes, Madrid, Spain, discussed how and when to use immunotherapy in patients with TNBC, focusing on toxicities associated with this treatment approach. Dr Cortes highlighted that targeting the immune system is an active therapeutic approach for a subgroup of patients with metastatic TNBC. Combining chemotherapy and immunotherapy appears to be a robust approach in metastatic TNBC given that chemotherapy induces multiple immunomodulatory changes in the tumour environment that may influence the effectiveness of immunotherapy. Atezolizumab has been approved in combination with nab-paclitaxel in patients with metastatic TNBC whose tumours are positive for PD-L1 expression (≥1%) on immune infiltrate, evaluated by the VENTANA PD-L1 (SP142) antibody. Pembrolizumab in combination when paclitaxel, nab-paclitaxel or carboplatin plus gemcitabine has demonstrated improved PFS when PD-L1 expression was ≥10 (combined positive score). However, the optimal platform for assessing PD-L1 status remains unknown. Other biomarkers that can identify a broader group of patients who could benefit from this therapeutic approach are urgently needed to define an optimal ‘breast cancer immunogram’.

Immune-related adverse events (irAEs) are closely associated with the known mechanisms of action of both PD-1 and PD-L1 antibodies. Loss of immune tolerance to self-antigens is principally T-cell mediated. Other immune cells may play a role in the development of irAEs, including B cells secreting antibodies, granulocytes secreting inflammatory mediators, and cytokines. Toxicities with anti-PD-1/PD-L1 are less common and less severe as compared with anti-CTLA-4 agents. irAEs require a unique approach in educating patients, monitoring, and managing toxicity.

“irAEs can be understood on the basis of immune mechanisms that lead to the hyperactivation of T cells.”

Javier Cortes, Madrid, Spain

Assess for signs of irAEs before each immunotherapy treatment, avoid delays in recognition and intervention, management is based on severity of symptoms - corticosteroids and other immunosuppressants can manage most irAEs, dose reduction is not recommended, patient education is critical

General principles of immune-related adverse event (irAE) management

Closing Remarks

SABCS 2020 was a successful meeting with attendees able to remotely access new data and clinical insights, and ‘virtually’ interact with clinical experts. This will hopefully stimulate new ways of thinking and ultimately translate into optimal care for the breast cancer patient. In addition, the virtual format provided the opportunity for participants, particularly those outside the US, to attend SABCS perhaps for the first time. This revised format for 2020 also enabled more institutions around the world to conveniently gain access to ‘on demand’ meeting content.