Integrated molecular pathway analysis informs a synergistic combination therapy targeting PTEN/PI3K and EGFR pathways for basal-like breast cancer

She, Qing-Bai; Gruvberger-Saal, Sofia K.; Maurer, Matthew; Chen, Yilun; Jumppanen, Mervi; Su, Tao; Dendy, Meaghan; Lau, Ying-Ka Ingar; Memeo, Lorenzo; Horlings, Hugo M.; van de Vijver, Marc J.; Isola, Jorma; Hibshoosh, Hanina; Rosen, Neal; Parsons, Ramon; Saal, Lao H.

doi:10.1186/s12885-016-2609-2

Table 3 Correlation of PI3K Pathway Lesions to Other Clinicopathological Markers

From: Integrated molecular pathway analysis informs a synergistic combination therapy targeting PTEN/PI3K and EGFR pathways for basal-like breast cancer

	ER+	ER–	n	P	PgR+	PgR –	n	P	p53 mut	p53 wt	n	P	CK5/14 +	CK5/14 –	n	P	Grade 1	Grade 2	Grade 3	n	P	<20 mm	20–49 mm	50 mm+	n	P	Node+	Node –	n	P	S–phase ≤6 %	S–phase 6-10 %	S–phase ≥10 %	n	P	Basal-like	HER2	Normal-like	LumA	LumB	n	P
PTEN IHC–	11	14	107	0.0007	8	17	107	0.0003	15	9	106	0.006	11	13	106	<0.0001	0	2	23	106	0.002	3	14	8	107	0.002	14	8	97	0.392	4	1	13	85	0.062	11	2	2	0	2	86	0.0003
PTEN IHC+	65	17			59	23			26	56			7	75			8	27	46			28	47	7			40	35			24	15	28			11	6	8	31	13
PTEN mut	2	2	112	0.334	2	2	112	0.600	3	1	112	0.115	2	2	105	0.061	0	0	4	111	0.166	0	3	1	111	0.175	2	2	101	0.855	1	0	2	91	0.708	3	0	0	0	0	94	0.048
PTEN wt	78	30			68	40			39	69			15	86			8	31	68			35	58	14			53	44			30	16	42			20	10	10	34	17
PTEN abrogated	12	14	107	0.001	9	17	107	0.0007	16	9	106	0.003	11	14	106	<0.0001	0	2	24	106	0.0012	3	14	9	107	0.0005	15	8	97	0.291	5	1	13	85	0.135	12	2	2	0	2	86	<0.0001
PTEN normal	64	17			58	23			25	56			7	74			8	27	45			28	47	6			39	35			23	15	28			10	6	8	31	13
HER2+	13	10	113	0.092	13	10	113	0.548	13	10	112	0.058	3	18	108	0.740	1	7	15	112	0.806	7	13	3	113	0.979	13	8	103	0.437	3	3	10	90	0.177	3	7	3	2	3	92	0.0003
HER2–	67	23			57	33			31	58			15	72			7	24	58			28	50	12			43	39			26	14	34			19	3	8	31	13
EGFR+	4	23	112	<0.0001	5	22	112	<0.0001	19	8	111	<0.0001	15	11	109	<0.0001	0	2	25	111	0.0008	6	16	5	112	0.216	13	9	102	0.583	5	3	14	89	0.112	16	3	1	0	0	91	<0.0001
EGFR–	74	11			63	22			24	60			4	79			8	29	47			28	47	10			42	38			25	13	29			7	6	10	32	16
PIK3CA mut	22	7	116	0.480	21	8	116	0.153	11	18	115	0.966	4	22	109	0.753	4	10	14	115	0.027	10	16	3	115	0.568	16	11	105	0.474	13	3	9	93	0.042	5	3	5	12	3	95	0.446
PIK3CA wt	60	27			50	37			33	53			15	68			4	22	61			26	48	12			40	38			18	14	36			18	7	6	22	14
INPP4B low	10	10	94	0.012	12	8	94	0.773	10	10	93	0.292	6	13	88	0.057	3	3	14	94	0.954	8	7	5	93	0.928	9	10	85	0.750	5	6	3	73	0.235	11	1	1	7	0	94	0.003
INPP4B high	58	16			47	27			27	46			9	60			5	24	45			19	47	7			34	32			20	9	30			12	9	10	26	17
Any PTEN/PI3K/INPP4B	44	17	95	0.434	37	24	95	0.333	24	36	94	0.305	11	47	89	0.467	2	13	45	94	0.004	18	34	8	94	0.561	27	27	84	0.379	20	6	26	78	0.594	14	4	6	18	9	83	0.892
None PTEN/PI3K/INPP4B	27	7			24	10			10	24			4	27			5	13	16			8	21	5			18	12			6	8	12			6	2	5	12	7
Any PTEN/PI3K/INPP4B/EGFR/HER2	47	33	106	0.0004	43	37	106	0.014	40	39	105	0.0004	19	56	101	0.0044	6	17	56	105	0.081	21	47	12	106	0.268	40	33	96	0.559	23	10	30	84	0.319	23	10	9	16	8	92	<0.0001
None PTEN/PI3K/INPP4B/EGFR/HER2	25	1			21	5			3	23			0	26			2	12	12			9	15	2			11	12			4	6	11			0	0	2	16	8

Footnote: Definitions are as in Table 2

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