ESF1

Summary

ESF1 (ESF1 nucleolar pre-rRNA processing protein, HGNC:15898) is a protein-coding gene on chromosome 20p12.1, encoding ESF1 homolog (Q9H501). May constitute a novel regulatory system for basal transcription. It is a selective cancer dependency (DepMap: 88.9% of cell lines).

Enables RNA binding activity. Predicted to be involved in rRNA processing. Located in extracellular space.

Source: NCBI Gene 51575 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 138 total
• Cancer dependency (DepMap): dependent in 88.9% of screened cell lines
• MANE Select transcript: NM_001276380

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15898
Approved symbol	ESF1
Name	ESF1 nucleolar pre-rRNA processing protein
Location	20p12.1
Locus type	gene with protein product
Status	Approved
Aliases	bA526K24.1
Ensembl gene	ENSG00000089048
Ensembl biotype	protein_coding
OMIM	618765
Entrez	51575

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000202816, ENST00000617257, ENST00000874578, ENST00000874579, ENST00000919901, ENST00000919902, ENST00000919903, ENST00000919904, ENST00000942288, ENST00000942289

RefSeq mRNA: 2 — MANE Select: NM_001276380 NM_001276380, NM_016649

CCDS: CCDS13117

Canonical transcript exons

ENST00000617257 — 14 exons

Exon	Start	End
ENSE00000659759	13733721	13733842
ENSE00000659760	13759692	13759853
ENSE00000659761	13766777	13766924
ENSE00000659762	13769907	13770021
ENSE00000659764	13771331	13771483
ENSE00000659765	13772515	13772615
ENSE00000659766	13775157	13775270
ENSE00000659767	13775873	13776270
ENSE00000859132	13728378	13728465
ENSE00000990127	13718908	13718984
ENSE00000990128	13717368	13717514
ENSE00001214762	13782504	13783183
ENSE00003910380	13714325	13715167
ENSE00003912821	13784880	13784919

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3590 / max 559.7910, expressed in 1585 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186470	6.5177	1552
186468	0.6278	253
186469	0.2134	69

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.39	gold quality
sperm	CL:0000019	97.70	gold quality
buccal mucosa cell	CL:0002336	96.86	gold quality
cranial nerve II	UBERON:0000941	96.58	gold quality
oocyte	CL:0000023	96.50	gold quality
tendon of biceps brachii	UBERON:0008188	95.44	gold quality
medial globus pallidus	UBERON:0002477	95.03	gold quality
tendon	UBERON:0000043	94.96	gold quality
globus pallidus	UBERON:0001875	94.86	gold quality
calcaneal tendon	UBERON:0003701	94.78	gold quality
lateral globus pallidus	UBERON:0002476	94.56	gold quality
male germ cell	CL:0000015	94.31	gold quality
visceral pleura	UBERON:0002401	94.20	gold quality
sural nerve	UBERON:0015488	93.96	gold quality
parietal pleura	UBERON:0002400	93.44	gold quality
tibia	UBERON:0000979	93.29	gold quality
pericardium	UBERON:0002407	93.13	gold quality
inferior vagus X ganglion	UBERON:0005363	92.85	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.48	gold quality
pleura	UBERON:0000977	92.13	gold quality
subthalamic nucleus	UBERON:0001906	91.60	gold quality
blood vessel layer	UBERON:0004797	91.54	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.39	gold quality
mammary duct	UBERON:0001765	91.37	gold quality
substantia nigra pars compacta	UBERON:0001965	91.22	gold quality
medulla oblongata	UBERON:0001896	91.21	gold quality
hair follicle	UBERON:0002073	91.19	gold quality
epithelium of mammary gland	UBERON:0003244	90.96	gold quality
pons	UBERON:0000988	90.92	gold quality
corpus callosum	UBERON:0002336	90.81	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting ESF1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-12123	99.52	71.79	2990

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 88.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• The Rattus rattus ABT1-associated protein formed a complex with ABT1 and suppressed activation of Pol II-directed transcription in mammalian cells. It binds and negatively regulates ABT1. (PMID:15660422)
• Human RPF1 and ESF1 in Pre-rRNA Processing and the Assembly of Pre-Ribosomal Particles: A Functional Study. (PMID:38391939)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	esf1	ENSDARG00000008740
mus_musculus	Esf1	ENSMUSG00000045624
rattus_norvegicus	Esf1	ENSRNOG00000004777
drosophila_melanogaster	CG11417	FBGN0024364
caenorhabditis_elegans		WBGENE00010231

Protein

Protein identifiers

ESF1 homolog — Q9H501 (reviewed: Q9H501)

Alternative names: ABT1-associated protein

All UniProt accessions (2): Q9H501, A0A087WX71

UniProt curated annotations — full annotation on UniProt →

Function. May constitute a novel regulatory system for basal transcription. Negatively regulates ABT1.

Subunit / interactions. Interacts with ABT1. Forms a complex with ABT1 and suppresses the ABT1-induced activation of polymerase II-directed transcription in mammalian cells.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm.

Similarity. Belongs to the ESF1 family.

RefSeq proteins (2): NP_001263309, NP_057733 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012580	NUC153	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR039754	Esf1	Family
IPR056750	RRM_ESF1	Domain

Pfam: PF08159, PF25121

UniProt features (58 total): modified residue 22, sequence conflict 13, compositionally biased region 12, region of interest 5, sequence variant 3, initiator methionine 1, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H501-F1	64.81	0.09

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (22): 2, 75, 77, 79, 82, 134, 153, 179, 180, 198, 296, 298, 311, 312, 313, 614, 657, 663, 693, 694 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 146 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WEI_MYCN_TARGETS_WITH_E_BOX, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GGCKCATGS_UNKNOWN, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, BERENJENO_TRANSFORMED_BY_RHOA_UP, GOCC_NUCLEOLUS, BENPORATH_ES_1, HAMAI_APOPTOSIS_VIA_TRAIL_UP, PUIFFE_INVASION_INHIBITED_BY_ASCITES_DN, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_UP

GO Biological Process (1): rRNA processing (GO:0006364)

GO Molecular Function (1): RNA binding (GO:0003723)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), nucleolus (GO:0005730), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
nucleic acid binding	1
cellular anatomical structure	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2283 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ESF1	ABT1	Q9ULW3	876
ESF1	EMG1	Q92979	677
ESF1	DDX49	Q9Y6V7	660
ESF1	UTP25	Q68CQ4	639
ESF1	PDCD11	Q14690	634
ESF1	NOP56	O00567	564
ESF1	BYSL	Q13895	564
ESF1	UTP20	O75691	555
ESF1	KRI1	Q8N9T8	553
ESF1	DDX10	Q13206	532
ESF1	UTP4	Q969X6	532
ESF1	HEATR1	Q9H583	521
ESF1	DHX8	Q14562	475
ESF1	UTP18	Q9Y5J1	461
ESF1	SLX4IP	Q5VYV7	460

IntAct

115 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
ARL3	UNC119B	psi-mi:“MI:0914”(association)	0.730
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
RBM34	RRP8	psi-mi:“MI:0914”(association)	0.640
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPLP0	GTPBP10	psi-mi:“MI:0914”(association)	0.530
NPM1	WDR46	psi-mi:“MI:0914”(association)	0.480
ESF1	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
ADAM19	ESF1	psi-mi:“MI:0915”(physical association)	0.370
Srp72		psi-mi:“MI:0914”(association)	0.350
Faap100	CDKN2A	psi-mi:“MI:0914”(association)	0.350
CDK2AP1	MTA3	psi-mi:“MI:0914”(association)	0.350
ZMYND8	MTA3	psi-mi:“MI:0914”(association)	0.350
ITPKB	PDE4A	psi-mi:“MI:0914”(association)	0.350
HNRNPU		psi-mi:“MI:0914”(association)	0.350
Nhsl1	H3-3B	psi-mi:“MI:0914”(association)	0.350
Bcl7c	SMARCD2	psi-mi:“MI:0914”(association)	0.350
GAR1	TAF1	psi-mi:“MI:0914”(association)	0.350
FBXO7	ELOC	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (180): ESF1 (Affinity Capture-RNA), ESF1 (Affinity Capture-MS), AATF (Co-fractionation), DDX52 (Co-fractionation), ESF1 (Co-fractionation), ESF1 (Co-fractionation), KIAA0020 (Co-fractionation), MPHOSPH10 (Co-fractionation), SEPT7 (Co-fractionation), UTP3 (Co-fractionation), ESF1 (Affinity Capture-MS), ESF1 (Affinity Capture-MS), ESF1 (Affinity Capture-MS), ESF1 (Affinity Capture-MS), ESF1 (Affinity Capture-MS)

ESM2 similar proteins: F4JP52, F4JW79, F4K4D6, F4K4Y5, I1HNB2, O04608, O23063, O24591, O48802, O49595, P05221, P06748, P07222, P13084, P16039, P35659, P91753, Q0WNR6, Q1HTZ8, Q1HTZ9, Q1PEP5, Q3T160, Q56WH4, Q61937, Q63ZM9, Q6AXS3, Q6DJ13, Q6V9I6, Q7TNV0, Q7XTT4, Q84JB7, Q8GUP3, Q8LDF9, Q8LJS2, Q8RXT5, Q94C59, Q94IK2, Q9C8J7, Q9FVE6, Q9H501

Diamond homologs: O74828, Q06344, Q3V1V3, Q756J5, Q76MT4, Q9H501

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 152 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Eukaryotic Translation Initiation	5	15.0×	5e-04
Cap-dependent Translation Initiation	5	15.0×	5e-04
SARS-CoV-1 modulates host translation machinery	5	15.0×	5e-04
Influenza Viral RNA Transcription and Replication	7	14.6×	4e-05
rRNA modification in the nucleus and cytosol	8	14.5×	2e-05
Influenza Infection	8	13.7×	2e-05
Nonsense-Mediated Decay (NMD)	6	13.6×	3e-04
Eukaryotic Translation Elongation	5	13.5×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	12	20.6×	4e-10
cytoplasmic translation	9	12.5×	2e-05
rRNA processing	7	7.5×	7e-03
translation	8	6.2×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

138 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	107
Likely benign	13
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2275 predictions. Top by Δscore:

Variant	Effect	Δscore
20:13715163:TTTAC:T	acceptor_gain	1.0000
20:13715164:TTAC:T	acceptor_gain	1.0000
20:13715165:TAC:T	acceptor_gain	1.0000
20:13715166:AC:A	acceptor_gain	1.0000
20:13715167:CC:C	acceptor_gain	1.0000
20:13715168:C:CC	acceptor_gain	1.0000
20:13715177:C:CT	acceptor_gain	1.0000
20:13715178:A:T	acceptor_gain	1.0000
20:13717363:GTTAC:G	donor_loss	1.0000
20:13717364:TTAC:T	donor_loss	1.0000
20:13717365:TACCT:T	donor_loss	1.0000
20:13717366:A:T	donor_loss	1.0000
20:13717378:T:TA	donor_gain	1.0000
20:13717387:AATT:A	donor_gain	1.0000
20:13717390:T:A	donor_gain	1.0000
20:13717394:T:TA	donor_gain	1.0000
20:13717510:TCAGC:T	acceptor_gain	1.0000
20:13717511:CAGC:C	acceptor_gain	1.0000
20:13717511:CAGCC:C	acceptor_gain	1.0000
20:13717512:AGC:A	acceptor_gain	1.0000
20:13717512:AGCCT:A	acceptor_loss	1.0000
20:13717513:GC:G	acceptor_gain	1.0000
20:13717513:GCC:G	acceptor_loss	1.0000
20:13717514:CCTG:C	acceptor_gain	1.0000
20:13717515:C:CA	acceptor_loss	1.0000
20:13717515:C:CC	acceptor_gain	1.0000
20:13717516:T:A	acceptor_loss	1.0000
20:13717517:G:C	acceptor_gain	1.0000
20:13717517:G:GC	acceptor_gain	1.0000
20:13717525:C:CT	acceptor_gain	1.0000

AlphaMissense

3089 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:13759699:C:A	W607C	0.999
20:13759699:C:G	W607C	0.999
20:13759701:A:G	W607R	0.999
20:13759701:A:T	W607R	0.999
20:13766912:A:G	W511R	0.999
20:13766912:A:T	W511R	0.999
20:13771334:A:G	L467P	0.998
20:13771351:A:C	S461R	0.998
20:13771351:A:T	S461R	0.998
20:13771353:T:G	S461R	0.998
20:13771427:G:T	A436E	0.998
20:13775237:A:G	W357R	0.998
20:13775237:A:T	W357R	0.998
20:13766910:C:A	W511C	0.997
20:13766910:C:G	W511C	0.997
20:13771428:C:G	A436P	0.997
20:13771445:C:G	R430P	0.997
20:13775161:A:T	V382D	0.997
20:13775251:A:T	V352D	0.997
20:13770016:A:T	I470K	0.996
20:13771397:G:T	A446D	0.996
20:13733777:A:G	W632R	0.995
20:13733777:A:T	W632R	0.995
20:13771462:T:A	R424S	0.995
20:13771462:T:G	R424S	0.995
20:13775235:C:A	W357C	0.995
20:13775235:C:G	W357C	0.995
20:13775254:G:T	A351E	0.995
20:13733775:C:A	W632C	0.994
20:13733775:C:G	W632C	0.994

dbSNP variants (sampled 300 via entrez): RS1000042373 (20:13758442 A>G), RS1000076354 (20:13731475 T>C), RS1000151567 (20:13739151 A>G), RS1000158363 (20:13762082 T>A), RS1000200503 (20:13751409 G>A), RS1000207875 (20:13758282 T>C), RS1000262687 (20:13747377 G>A), RS1000284498 (20:13760181 T>A,C), RS1000302884 (20:13757917 T>A), RS1000328247 (20:13734430 A>C), RS1000403129 (20:13778641 A>G), RS1000516463 (20:13742556 C>A,T), RS1000549012 (20:13748963 T>C), RS1000620003 (20:13726570 A>G), RS1000631523 (20:13749198 T>C)

Disease associations

OMIM: gene MIM:618765 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
nickel sulfate	decreases expression	1
coumarin	increases phosphorylation	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Leflunomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Caffeine	decreases phosphorylation	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Phthalic Acids	decreases methylation	1
Plant Extracts	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

11 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery