Overview of diagnostic/targeted treatment combinations in personalized medicine for breast cancer patients

Figures & data

Table 1 Treatment options, current, and future biomarkers in different subgroups of breast cancer

Breast cancer population	Subtypes	Detection method	Current treatment	Markers of response	Markers of resistance	Exploitable markers
ER+ and/or PgR+	Luminal A	Gene expression profile	HT alone	High ER levels	ER levels <10%	ER-alpha aberrations
	Luminal B	Ki67 label index >14%	HT + mTOR inhibitors	High Ki67 levels	HER2 overexpression	FGFR 1
		Lack of expression of PgR	CT		Low Ki67 levels	PI3K/PTEN/CCND1 alterations
HER2+ ER+	HER2-enriched	Gene expression profile	CT + anti-HER2 (single or double block) ± mTOR inhibitors	High Ki67 levels	p95 HER2	D16 HER2
	Luminal A	HER2 amplification			High ER levels	Immune metagene
	Luminal B	ER overexpression	HT + anti-HER2			ER-alpha aberrations
		Ki67 label index > 14%				FGFR 1
						PI3K/PTEN/CCND1 alterations
HER2+ ER-	HER2-enriched	Gene expression profile	CT + anti-HER2 (single or double block) ± mTOR inhibitors	High Ki67 levels	p95 HER2	D16 HER2
		HER2 amplification				Immune metagene
						FGFR 1
						PI3K/PTEN/CCND1 alterations
						IFNG
						STAT 1
Triple negative breast cancer	Basal-like	Gene expression profile	CT	High Ki67 levels		BRCA1 mutations
	Nonbasal-like	Lack of expression of ER and PgR				TOP 2A
		Lack of expression of HER2				P53 mutations
						BCL2
						TIL
						FGFR 2
						NOTCH
						Caveolin 1

Abbreviations: ER, estrogen receptor; PgR, progesterone receptor; HT, hormonal therapy; CT, chemotherapy; FGFR 1, fibroblast growth factor receptor 1; PI3K, phosphatidylinositol 3-kinase; PTEN, phosphatase and tensin homolog; CCND1, cyclin D1; HER, human epidermal growth factor; mTOR, mammalian target of rapamycin; IFNG, interferon gamma; STAT1, signal transducers and activators of transcription 1; D16 HER2, HER 2 splice variant lacking exon 16; BRCA1, breast cancer type 1 susceptibility protein; TOP 2A, topoisomerase 2A; TIL, tumor infiltrating lymphocyte.

Figure 1 Schematic representation of the main targeted pathways and their inhibitory drugs in breast cancer treatment.

Note: Schematic based on a knowledge of the underlying genetic changes and downstream biological consequences.
Abbreviations: E2, estradiol; AI, aromatase inhibitors; EGF, epidermal growth factor; HER, human epidermal growth factor; ER, estrogen receptor; PTEN, phosphatase and tensin homolog; PI3Ki, PI3 kinase inhibitors (ie, BKM120, GDC0941, XL147, BYL719, BEZ235); TK, tyrosine kinase; T-DM1, trastuzumab emtansine; AKT, serine/threonine-specific protein kinase; mTOR, mammalian target of rapamycin; RAS, reticular activating system; MEK, mitogen-activated extracellular signal-regulated kinase; MAPK, mitogen-activated protein kinase; FGFRi, fibroblast growth factor receptor inhibitors (ie, dovitinib, intedanib, brivanib).