Visceral crisis in metastatic breast cancer: an old concept with new perspectives

Andrade, Matheus de Oliveira; Bonadio, Renata Rodrigues da Cunha Colombo; Diz, Maria Del Pilar Estevez; Testa, Laura

doi:10.1016/j.clinsp.2024.100362

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Sumário

Review articles • Clinics 79 • 2024 • https://doi.org/10.1016/j.clinsp.2024.100362 copy

Visceral crisis in metastatic breast cancer: an old concept with new perspectives

Authorship SCIMAGO INSTITUTIONS RANKINGS

Highlights

Visceral crisis in metastatic breast cancer is associated with a dismal prognosis.
There is a lack of objective clinical criteria in the definition of visceral crisis.
Visceral crisis management is currently based on limited retrospective evidence and expert opinions.
The role of chemotherapy as the treatment of choice for visceral crisis has been recently questioned.

Abstract

Visceral Crisis (VC) in breast cancer is a critical scenario when the burden of metastatic disease results in rapid deterioration of organ functions. There are no widely accepted objective clinical criteria for the definition of VC, and different studies have reported diverse clinical conditions such as visceral crises. Diagnosis of VC is associated with a dismal prognosis and the management of this condition is currently based on limited retrospective evidence and expert opinions. International guidelines have recommended cytotoxic polychemotherapy in the management of VC, to achieve rapid symptomatic control and preserve organ function. Nevertheless, in the case of hormone receptor-positive breast cancer, the role of chemotherapy as the treatment of choice for VC has been recently questioned, since endocrine therapy plus CDK4/6 inhibitors yielded similar response rates, with better quality of life. For HER2-positive and triple-negative breast cancer, combined chemotherapy (plus HER2-directed therapy for HER2-positive) remains a standard option for VC, but novel effective drugs such as antibody-drug conjugates are emerging and their role in the VC context shall soon be elucidated. This review aims to critically discuss the definition, prognosis, management, and future directions regarding the visceral crisis in metastatic breast cancer.

Keywords
Breast cancer; Neoplasm metastasis; Chemotherapy

Reference	n (patients with VC)	BC subtype	VC type	Prior palliative treatment for ABC before VC	VC Treatment regimen	Efficacy Outcomes	Prognostic factors	CT in last weeks of life
Franzoi et al. 2021⁶6 Franzoi MA, Saúde-Conde R, Ferreira SC, Eiger D, Awada A, de Azambuja E. Clinical outcomes of platinum-based chemotherapy in patients with advanced breast cancer: An 11-year single institutional experience. Breast. 2021;57:86-94.	261	HR+/HER2- (63.6 %)	Liver (51.3 %)	None: 12.3 %	Platinum-based CT (100 %)	mOS 3.7 months	ECOG-PS≥2	42.6 % (last 4 weeks before death)
		HR+/HER2- (63.6 %)	Lung (17.2 %)	1‒3 prior treatment lines: 44.4 %		ORR 27.2 %	Hyperbilirubinemia
		HR+/HER2+ (6.5 %)	Brain (10.7 %)	1‒3 prior treatment lines: 44.4 %			> 3 previous treatment lines
		HR-/HER2+ (8 %)	Peritoneum (9.5 %)	> 3 prior treatment lines: 43.3 %			Non-resolution of VC
		TNBC (21.8 %)	Meninges (8.4 %)
		TNBC (21.8 %)	Others (2.6 %)
Yang et al. 2022⁴4 Yang R, Lu G, Lv Z, Jia L, Cui J. Different treatment regimens in breast cancer visceral crisis: a retrospective cohort study. Front Oncol. 2022;12(October):1-11.	133	HR+/HER2- (69.2 %)	Liver (50.4 %)	NR	Trastuzumab + Pertuzumab (12.78 %)	mOS 11.2 months	ECOG-PS	NR
		HR+/HER2- (69.2 %)	Bone marrow (24.8 %)		Trastuzumab + Pertuzumab (12.78 %)	mOS 11.2 months	Type of VC
		HR-/HER2+ (15 %)	Meninges (15.8 %)		Antibody-Drug Conjugate (2.26 %)	mPFS 5.2 months
		TNBC (15.8 %)	Lung (7.5 %)		Paclitaxel (21.05 %)
			SVCS (1.5 %)		Paclitaxel (21.05 %)
					Platinum (19.55 %)
					Gemcitabine (18.79 %)
					Eribulin (2.26 %)
					AI (11.28 %)
					CDK4/6 inhibitors+AI (11.28 %)
					CDK4/6+ Fulvestrant (0.75 %)
Funasaka et al. 2021⁹9 Funasaka C, Naito Y, Kusuhara S, Nakao T, Fukasawa Y, Mamishin K, et al. The efficacy and safety of paclitaxel plus bevacizumab therapy in breast cancer patients with visceral crisis. Breast. 2021;58:50-6.	44	HR+/HER2- (80 %)	Lung (66 %)	None: 68 %	Paclitaxel + bevacizumab (100 %)	mOS 10.6 months	ECOG-PS≥2	NR
		HR+/HER2- (80 %)	Liver (23 %)	CT: 1 line: 14 %; ≥2 lines: 18 %		mOS 10.6 months	LDH≥300
		TNBC (20 %)	Bone marrow (16 %)	CT: 1 line: 14 %; ≥2 lines: 18 %		ORR 41 %	≥2nd-line CT
			Bone marrow (16 %)	ET: NR
			SVCS (5 %)	ET: NR
Sbitti et al. 2017⁸8 Sbitti Y, Slimani K, Debbagh A, Mokhlis A, Kadiri H, Laraqui A, et al. Visceral crisis means short survival among patients with luminal a metastatic breast cancer: a retrospective cohort study. World J Oncol. 2017;8(4):105-9.	35	HR+/HER2- (100 %)	Liver (55 %)	2 lines of ET: 100 %	Epirubicine and cyclophosphamide (25 %)	mOS 4.7 weeks (5.8 weeks for CT; 6.2 weeks for BSC)	ECOG-PS	65 % (last 5 weeks before death)
			Lung (35 %)		Paclitaxel and bevacizumab (20 %)
			Meninges (20 %)		Paclitaxel and bevacizumab (20 %)
					Docetaxel (20 %)
					BSC (34.3 %)
Sakin et al. 2019¹⁵15 Sakin A, Sakalar T, Sahin S, Yasar N, Demir C, Geredeli C, et al. Factors affecting survival and treatment efficacy in breast cancer patients with bone marrow metastasis. Breast J. 2019;26(4):815-8.	30	HR+ (70 %)	Bone marrow (100 %)	Median of 2.5 treatment lines	Paclitaxel (60 %)	mOS 9 months	NR	NR
		HER2+ (13.3 %)			Cisplatin (13.3 %)
		HER2+ (13.3 %)			Eribulin (10 %)
		TNBC (13.3 %)			Capecitabine (6.7 %)
		TNBC (13.3 %)			BSC (10 %)
Kopp et al. (2011)¹⁶16 Kopp HG, Krauss K, Fehm T, Staebler A, Zahm J, Vogel W, et al. Symptomatic bone marrow involvement in breast cancer - clinical presentation, treatment, and prognosis: a single institution review of 22 cases. Anticancer Res. 2011;31(11):4025-30.	22	HR+ (72.7 %)	Bone marrow (100 %)	NR	Docetaxel + Doxorubicin (27.3 %)	mOS 11 months	NR	NR
		HER2 (13.6 %)
		TNBC (9.1 %)
					Gemcitabine + vinorelbin (22.7 %)
					Doxorubicin liposomal, capecitabine, cyclophosphamide, docetaxel, gemcitabine, paclitaxel (4.5 %)
Sharma et al. (2003)³³33 Sharma RA, Decatris MP, Santhanam S, Roy R, Osman AE, Clarke CB, et al. Reversibility of liver failure secondary to metastatic breast cancer by vinorelbine and cisplatin chemotherapy. Cancer Chemother Pharmacol. 2003;52(5):367-70.	11	HR+ (54.5 %)	Liver (100 %)	Taxane (63.6 %)	Cisplatin + vinorelbine (100 %)	mOS 6.5 months	NR	NR
		HER2+ (36.4 %)		Anthracycline (36.4 %)		ORR 63.6 %
		TNBC: NR		Trastuzumab (36.4 %)
		TNBC: NR		Other (18.2 %)

Clinical Trials ID	Design	Population	Intervention	Primary Outcome	Main Secondary Outcomes	Status
NCT04681768	Single-arm phase II	HR+/HER2- ABC with symptomatic visceral metastases or high tumor burden	Abemaciclib + ET (1st line)	ORR	DCR, DoR, PFS, TTF, AE, PRO	Recruiting
NCT05431504	Single-arm phase II	HR+/HER2- ABC with VC	Dalpiciclib + ET (1st line)	6-month OS	OS, PFS, TTF, ORR, CBR, DoR, TTR, AE	Not yet recruiting

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[1] Declaration of competing interest

The authors declare no conflicts of interest.