Locoregional treatment of early breast cancer with isolated tumor cells or micrometastases on sentinel lymph node biopsy

Table 1 Incidence of micrometastatic lymph-nodes among positive sentinel lymph nodes

Ref.	Population	n	ITCs (%)	MMs (%)	ITCs + MMs	Macrometastases
Houvenaeghel et al[5]	cT0-2N0	2413	13	33	46	54
Yi et al[8]	Positive SLNB	26986	-	25	-	75
Madsen et al[9]	cT1-2N0	517	10	24	34	66

SEER: Surveillance, epidemiology and end results; SLNB: Sentinel lymph node biopsy; ITC: Isolated tumor cells; MMs: Micrometastases.

Table 2 Distribution between pN0(i+) and pN1mi

Ref.	n	ITCs (%)	MMs (%)
Houvenaeghel et al[5]	1099	28	72
van Rijk et al[7]	253	42	58
Meretoja et al[13]	484	43	57
Tvedskov et al[14]	1881	16	84

ITC: Isolated tumor cells; MMs: Micrometastases.

Table 3 Rate of non-sentinel lymph node involved

Ref.	n	Rate of positive-NSLN
		IHC (%)	ITC (%)	pN1mi (%)	pN1a (%)
Houvenaeghel et al[15]	700	10.8	12.6	12	-
Meretoja et al[16]	1000	13.9	5.8	12.2	42.6
Viale et al[19]	1228	-	14.6	21.3	50.2
Tvedskov et al[20]	1881	-	9	18	-
Tvedskov et al[21]	900	-	13	17	-
Calhoun et al[24]	61	-	4.9	-	-

NSLN: Non-sentinel lymph node; IHC: Immunohistochemistry; ITC: Isolated tumor cells.

Table 4 Studies of prognostic factors for positive-non-sentinel lymph nodes in patients with micrometastasis or isolated tumor cells in sentinel lymph nodes

Ref.	n	Prognostic factors for positive NSLNs
		Tumor grade	Size of positive SLN	Proportion of positive SLN	Molecular subtype	Tumor size	Age	Nb of SLN examined	Presence of LVI	Histologic type	Multicentric tumor	ECE	Tumor location
Zhou et al[26]	130 (pN1mi 25%)	+	+	+	+	+	-	-	NR	NE	NE	NE	NE
Meretoja et al[16]	1000 (pN1mi 28%)	-	+	+	+	+	NR	NR	+	-	+	+	NE
Houvenaeghel et al[17]	909 (pN1mi 100%)	-	+	NR	NR	+	NR	NR	+	+	NE	NE	NE
Tvedskov et al[20]	1881 (pN1mi 100%)	-	NR	+	+	+	-	-	+	-	-	-	+

NSLN: Non-sentinel lymph node; SLN: Sentinel lymph node; LVI: Lymphovascular invasion; ECE: Evaluable capsular effraction; NR: Not reported; NE: Non evaluable.

Table 5 Recurrence-free survival, disease-specific survival and overall survival according to the burden of axillary positivity

LN status		LRR	RFS	DSS	OS
pN0/pN0(i+)	=		[3,34,36,39]		[3,32,34,36,38]
	>		[4,33]		[4]
pN0/pN1mi	=		[38]		[32,37,38]
	>	[30]	[4,29,32,33,34,36]	[32]	[4,29,30,34]
pN0(i+)/pN1mi	=		[33]
	>		[4]		[4]
pN1mi/pN1	=
	>				[30]

LN: Lymph node; LRR: Locoregional recurrence; RFS: Recurrence-free survival; DSS: Disease-specific survival; OS: Overall survival.

Table 6 Impact of completion axillary lymph node dissection on adjuvant therapy decision-making

Ref.	n	Variable analysed	Results						Conclusion
			Treatment arm	CT	HT	CT + HT	Any	Type
Montemurro et al[61]	566 pN0(i+)	Systemic treatments1	cALND	58	78	-	-	-	No difference
	pN1mi		ART	61	76	-	-	-
	pN1a		Absolute difference	3	2	-	-	-
Galimberti et al[23]	931 pN0(i+)	Systemic therapy	cALND	9	63	23	95	-	No difference
	pN1mi		SLNB	7	67	22	97	-
			Absolute difference	2	4	1	2	-
Aigner et al[58]	132 pN0(i+)	Administration of CT and type of CT	cALND	72.7	-	-	-	-	Relevant difference (type of CT)
	pN1mi		SLNB	77.3	-	-	-	-
	pN1a		Absolute difference	4.6	-	-	-	12.1
Pepels et al[41]	233 pN1mi	Systemic therapy	cALND	36.8	6.2	57	-	-	No difference
			SLNB	40.2	9.8	51	-	-
			Absolute difference	3.4	3.6	6	-	-
Sávolt et al[59]	474 pN0(i+)	Systemic therapy	cALND	78	87	65	-		No difference
	pN1mi		ART	69	89	58	-
	pN1a		Absolute difference	9	2	7	-
Montemurro et al[61]	321 pN0(i+)	Adjuvant chemotherapy	cALND	62	-	-	-	-	Relevant difference
	pN1mi		SLNB	52	-	-	-	-
	pN1a		Absolute difference	10	-	-	-	-

¹Proportion of patients treated with adjuvant systemic therapy, based on Adjuvant. Absolute differences in proportion of prescriptions appear in grey. cALND: Completion axillary lymph node dissection; CT: Chemotherapy; HT: Hormonal therapy; SLNB: Sentinel lymph node biopsy; ART: Axillary radiation therapy.