Abstract and Introduction
Abstract
Objective: The propose of this review to discuss of the systemic treatment options for newly diagnosed inflammatory breast cancer (IBC) including the recent data of immune checkpoint inhibitor, CDK4/6 inhibitor and anti-HER2 therapy. Aim to provide a pragmatic treatment in a gray area or concerning issues of real-world practice.
Background: IBC is a rare and aggressive disease. Upfront systemic treatment followed by surgery and radiation therapy or "Tri-modality" treatment is a standard of care for newly diagnosed IBC. Due to its rarity, the data of systemic treatment for IBC has been extrapolated mostly from non-IBC clinical trials.
Methods: We summarized the recent data of systemic treatment stratified by concerning topics and breast cancer subtypes. Some topics are less likely to have strong data from IBC clinical trial to supports. Therefore, we interpolate the non-IBC data to support our review.
Conclusions: IBC is challenging in the clinical management. The development of novel systemic treatment is urgently needed, especially for IBC-specific clinical trials.
Introduction
Term "Inflammatory breast cancer (IBC)" is an entity of aggressive form of breast cancer. Its aggressiveness shows poor survival outcome compared with those women diagnosed with non-IBC.[1–4] Interestingly, diagnostic criteria for IBC are based on clinical diagnosis, including the involvement at least one-third of the breast skin, a rapid onset of architectural changes such as erythema and edema (or peau d'orange).[5] These clinical characters may be due to the presence of tumor emboli within dermal lymphatics. Despite, tumor emboli are pathognomonic of IBC, but these are not required to make the diagnosis.[6] Only around 75% of diagnosed IBC present tumor emboli on pathological report.[7] Pathological analysis of IBC also shows the hypervascularity, around four times higher than non-IBC vascularity.[8] This is consisted with that IBC has higher levels of vascular endothelial growth factor D (VEGF-D), which is an angiogenesis marker.[9,10] Several studies reported the different higher mutations in gene expression between IBC and non-IBC, e.g., MYC, PIK3CA, ERBB2 and p53 mutation.[11–13] However, all of them have not been able to identified as a specific mutation for IBC.[10] Recently, the tumor microenvironment (TME) of IBC has been investigated and may play a crucial role in aggressiveness of IBC. Tumor-associated macrophages (TAMs) isolated from TME of IBC patients (especially M2 TAMs) produce several cytokines that promote progression and invasion of IBC cells.[9,10] Tumor-infiltrating lymphocytes also play an essential role in predictive chemotherapy response.[9,10] Finally, there are no the distinct genomic signatures that specifically distinguish IBC from non-IBC.[9] Implication, there are many specific intrinsic factors contribute to aggressive behavior, potential metastasis, and chemotherapy resistance of IBC.
Due to the aggressiveness of IBC as aforementioned, there are no de-escalation strategies for systemic treatment. It is not feasible to omit or short-course of IBC systemic treatment without affect to survival outcomes. Differently to non-IBC, de-escalation treatment is preferred in some situations. Recommended approach in newly diagnosed patient with IBC is upfront systemic treatment followed by surgery and radiation therapy (tri-modality) using a multidisciplinary team.[14,15] Due to the rarity, current standard guideline of IBC has been extrapolated mostly from the non-IBC clinical trials. Similarly to non-IBC, anthracycline- and taxane-based chemotherapy are still recommended as the backbone of chemotherapy regimens. For example, doxorubicin and cyclophosphamide (AC) regimen followed by taxane or instead of AC with fluorouracil, epirubicin and cyclophosphamide (EFC) regimen.[14,15] Targeted therapy or immune checkpoint inhibitor adding is considered depends on the IBC subtypes. Dual anti-human epidermal growth factor receptor 2 (HER2) blockade; trastuzumab and pertuzumab (HP), combined with chemotherapy has been recommended in HER2+ IBC. The propose of this review is to discuss the concerning topics that we are facing in the real-world practice of IBC. We discussed the treatment based on subtypes, mostly extrapolated form the non-IBC data. We present the following article in accordance with the Narrative Review reporting checklist (available at https://dx.doi.org/10.21037/cco-21-81).
Chin Clin Oncol. 2021;10(6):55 © 2021 AME Publishing Company
