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EPIDEMIOLOGY
Risk factors
increasing age: rate slows after menopause early menarche, late menopause , nulliparity atypical lobular or ductal hyperplasia(benign breast disease) early exposure to ionizing radiation long-term postmenopausal estrogen-replacement therapy alcohol consumption family history of breast ca.( most important )
- 5 to 10% occur in high-risk families - familial breast ca. syndrome : breast-ovarian cancer synd Li-Fraumeni synd Cowden's ds
BIOLOGY
Genetic abnormalities (1) familial breast ca
BRCA1 and BRCA2 germ line mutation . 50 to 85 % lifetime risk breast ca, ovarian ca, or both . genetic screening and counseling programs are ongoing
DIAGNOSTIC APPROACHES
Screening by mammography and physical examination - early diagnosis 25 to 30 % decrease in mortality over age of 50 yrs & probably in btw age of 40-50 yrs American Cancer Society, the National Cancer Institute recommend 1) annual mammography for > 40 yrs 2) high-risk families, with BRCA1 or BRCA2 mutant : at 25 yrs of age or 5 yrs earlier than earliest age at which breast ca diagnosed in family member Standard method for confirming diagnosis fine-needle aspiration or core needle biopsy
THERAPY
1. Primary Breast Cancer
Local disease without distant spread curable with local or regional treatment alone but, most pts have subclinical metastasis distant metastasis ultimately develop
Low (has all listed factors) < 1cm + Grade I > 35 yrs
High (at least one factor) > 2 cm Grade 2-3 < 35 yrs
Pt group Premenopausal, ER or PgR + ER and PgR Postmenopausal, ER or PgR + ER and PgR Elderly
ER: estrogen receptor, PgR: progesteron receptor TMF : tamoxifen, CTX : chemotherapy, NA : not applicapable
Pt group
Premenopausal, ER or PgR + ER and PgR Postmenopausal, ER or PgR + ER and PgR Elderly
TMF : tamoxifen, CTX : chemotherapy
Minimal/low risk
CTX + TMF CTX TMF + CTX CTX TMF
so, postop. RT indication only for high risk local recur. pts - large tumors > 5 cm - invading the skin of the breast or chest wall - many (> 4 ) positive axillary LNs
4) Preoperative Chemotherapy
large operable tumor 90% of tumor decrease in size by more than 50% lumpectomy possible survival benefit : no apparent advantage as compared with postop. chemotherapy
1) Hormonal intervention
- 20 to 35% response to initial hormonal therapy - 10 to 20% to second-line - 15 to 30% to another
Forth line
Androgens
Androgens or estrogens
2) Chemotherapy
- refractory to hormonal therapy 40 to 60% response to CMF - anthracycline-containing combination superior to CMF 50 to 80% response to FAC - new drugs vinorelbine( third-generation vinca alkaloid ) taxanes (paclitaxel and docetaxel) * Combinations of taxanes and anthracyclines responses in 40 to 94% complete remissions in 12 to 41%
Bone
- most common site of metastasis cause of substantial morbidity, complication
* Bisphosphonate (pamidronate and clodronate) add to chemotherapy or homonal therapy - reduce pain and complication - prolong survival free of bone-related event
3) High-Dose Chemotherapy
I. single cycle of high-dose combination of cytotoxic drug (usually alkylating agent) bone marrow damage is earliest limiting toxic effect - eliminated by reinfusing autologous hematopoietic stem cell
II. 2 to 4 cycles of cytotoxic-drug combination at dose higher than usual but not ablate bone marrow higher complete remission (40 to 60%) 15 to 25% free of cancer for 3 to 5 yrs
CHEMOPREVENTION
administration of adj. tamoxifen for 5yrs after primary Tx. - reduce incidence of contralat. breast ca. by 47% - endometrial ca. in twice - increase in thromboembolic event occured predominantly in older than 50 yrs * overall beneficial effect of tamoxifen outweighed adverse effect
NOVEL THERAPIES
HER-2/neu oncogene overexpressed in 20 to 30% - more aggressive - more resistant to chemotherapy 13% of metastatic breast ca with HER-2/neu - response to monoclonal antibody against extracellular domain of HER-2/neu oncoprotein chemotherapy combined with anti HER-2/neu antibody - increase response rate & prolongation of survival