DNA damage and breast cancer

Table 1 Categories of breast cancer and associated DNA lesions; breast cancer classification schemes, common DNA damage detected, and current clinical treatments¹

Breast cancer classification	Screening tests on biopsy sample	Current treatments	Expected outcomes
Hormone receptor positive	Immunohistochemistry, confirmed by CGH	Mostly SERM or SERD which may slow tumor growth. Drugs include: tamoxifen, raloxifene and fulvestrant	High survival rate if responsive to chemotherapy
TNBC	Immunohistochemistry	Surgery, radiation and chemotherapies which inhibit mitosis such as cisplatin	Initially sensitive to traditional chemotherapies and radiation therapy, but high recurrence rate thus poor survival rate[6,71,72]
HER-2 Over-expression	Immunohistochemistry, confirmed by CGH or FISH	HER-2 agonists such as trastuzamab or lapatinib and sometimes doxorubicin	Although this is a fast growing cancer if responsive to therapy HER2 agonists can half the rate of recurrence[5,73]
Luminal type A or B	Immunohistochemistry and micro-array or tissue array	As described above depending upon hormone receptor and growth factor receptor expression	5-year recurrence rate is lower and survival rate higher than for basal-like breast cancers[71,72]
BLBC	Immunohistochemistry and micro-array or tissue array	Similar to TNBC	5-year recurrence rate higher and survival rate lower than for luminal breast cancer types[71,72]

¹Categories based upon claudin-over-expressing, microRNA expression patterns or comparative genomic hybridization expression patterns are currently not widely utilized, thus standardized clinical protocols have been omitted from this table. TNBC: Triple negative breast cancer; BLBC: Basal-like breast cancer; SERM: Selective estrogen receptor modulators; SERD: Selective estrogen receptor down-regulators; CGH: Comparative genomic hybridization.

Table 2 Summary of DNA lesion type, repair mechanism and gene products

Repair mechanism	DNA lesion type	Genes or gene families involved in repair
NER	Distortions of DNA double helix or bulky adducts	Xeroderma pigmentosum related genes (XPA, XPC and others) and Cockayne’s syndrome related genes (ERCC6 and others)
BER	Small, non-helix-distorting nucleotide base lesions or single strand breaks	AP endonucleases, DNA glycosylases
MMR	Incorrectly paired nucleotides, insertions and deletion loops	MSH2, MLH1
HR	SSB and DSB	BRCA1/2, BRIT1, BLM
NHEJ	Chromosomal breaks, also to create genetic diversity for immune cells	Ku70, Ku80, DNA-PKcs, XRCC4

NER: Nucleotide excision repair; BER: Base-pair excision repair; HR: Homologous recombination; MMR: Mismatch repair; NHEJ: Non-homologous end joining; SSB: Single strand breaks; DSB: Double strand breaks.