Association between PIK3CA activating mutations and outcomes in early-stage invasive lobular breast carcinoma treated with adjuvant systemic therapy

FIGURE 1.

FIGURE 2.

FIGURE 3.

Simple Cox proportional hazards model for DMFS in the PIK3CA mutated patient cohort

Characteristic	HR	95% CI	Adj p
Age	0.99	0.96–1.02	1.0
Duration of TAM	0.92	0.75–1.14	1.0
Duration of AIs	1.07	0.90–1.28	1.0

Distribution of systemic therapy in all patients and according to PIK3CA mutation status

Systemic therapy	All ptsN (%)	PIK3CA mutated ptsN (%)	PIK3CA non-mutated ptsN (%)
None	12 (3)	5 (3)	7 (3)
ET only	249 (68)	115 (70)	134 (67)
ChT only	13 (4)	5 (3)	8 (4)
ET and ChT	91 (25)	39 (24)	52 (26)
None ET	25 (7)	10 (6)	15 (7)
ET with TAM	106 (29)	45 (27)	61 (30)
ET with AIs	127 (35)	54 (33)	73 (37)
Sequence TAM-AI	107 (29)	55 (34)	52 (26)
Median duration (range) of ET	5 (0.2–16.7)	5 (0.4–16.7)	5 (0.2–11.2)

Advanced Cox proportional hazards model for OS in the PIK3CA mutated patient cohort

Characteristic	HR	95% CI	Adj p
Age	1.05	1.02–1.08	0.014
Tumor size	1.38	0.90–2.10	0.84
Grade
G1	Ref
G2	1.41	0.59–3.38	1.0
G3	5.52	1.67–18.18	0.04
Ki-67	0.94	0.72–1.22	1.0
PR	1	0.99–1.01	1.0
PIK3CA status
Other than exon 20	Ref
Only exon 20	1.32	0.79–2.21	1.0
No. of positive axillary LNs	1.58	1.32–1.88	< 0.001
Duration of TAM	0.68	0.55–0.86	0.01
Duration of AI	0.73	0.60–0.88	0.01

Characteristics of the included patients and their tumors

Characteristic	All patients (n = 365; 100%)	PIK3CA mutated (n = 164; 45%)	PIK3CA non-mutated (n = 201; 55%)
Median age (range) (yrs)	62.8 (33–90)	63.1	62.4
Median tumor size (mm)	21	19	21
Nodal status
N0	209 (57)	100 (61)	109 (54)
N1	84 (23)	37 (22)	47 (23)
N2	26 (7)	1 (7)	15 (8)
N3	46 (13)	16 (10)	30 (15)
Tumor grade
G1	52 (14)	20 (12)	32 (16)
G2	270 (74)	134 (82)	136 (68)
G3	43 (12)	10 (6)	33 (16)
IHC* subtype
ER+/PR+/HER2−	299 (82)	136 (46)	159 (54)
ER+/PR−/HER2−	39 (11)	14 (36)	25 (64)
HER2 +	20 (6)	9 (45)	11 (55)
ER−/PR−/HER2−	7 (2)	2 (29)	5 (71)
Median Ki-67 (range) (%)	3 (1–50)	2.5 (1–50)	3 (1–40)
Mitotic score
M1	284 (78)	138 (84)	146 (73)
M2	55 (15)	19 (12)	36 (18)
M3	26 (7)	7 (4)	19 (9)
Presence of LVI	24 (7)	4 (2)	20 (10)
Median TILs (range) (%)	3 (1–50)	3	3
Median follow-up time (range) (yrs)	10.8 (0.1–18.6)	10.8	10.7

Advanced Cox proportional hazards model for DMFS in the PIK3CA mutated patient cohort

Characteristic	HR	95% CI	Adj p
Age	1.01	0.97–1.05	1.0
Tumor size	0.99	0.57–1.71	1.0
Grade
G1	Ref
G2	0.91	0.26–3.22	1.0
G3	1.03	0.16–6.83	1.0
Ki-67	1.35	0.93–1.95	1.0
PR	1	0.99–1.02	1.0
PIK3CA status
Other than exon 20	Ref
Only exon 20	2.19	1.01–4.80	0.582
No. of positive axillary LNs	1.64	1.30–2.06	< 0.001
Duration of TAM	1.02	0.81–1.29	1.0
Duration of AIs	1.06	0.87–1.28	1.0

Simple Cox proportional hazards model for OS in the PIK3CA mutated patient cohort

Characteristic	HR	95% CI	Adj p
Age	1.05	1.02–1.07	< 0.001
Duration of TAM	0.73	0.61–0.88	0.002
Duration of AIs	0.79	0.67–0.93	0.005