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risk factors for breast cancer & management of high-risk women

Etiology: Risk factors: 1) age > 50 (risk increases with age) 2) personal history a) colon cancer c) endometrial cancer d) ovarian cancer e) benign breast biopsy 3) family history a) breast cancer b) cancer family syndrome (i.e. Li Fraumeni syndrome) c) BRCA1 & BRCA2 gene mutations d) BRCA mutation negative patients in families with BRCA mutations - still at risk [12] - not at risk [25] e) defects in BRIP1 f) variations in PALB2 g) family history of prostate cancer [38] (RR=1.14) 4) genetic information adds modestly to risk prediction [18] 5) seemingly conflicting data regarding childbirth - nulliparity or low parity, age > 30 1st birth - risk increases in the 5 years following childbirth & remains elevated for 20 years [42] 6) early menarche 7) late menopause 8) exposure to ionizing radiation - radiation therapy in women < 30 years of age - mantle cell radiation for Hodgkin's disease [3] - mediastinal radiation therapy (risk begins within 8 years) [3] - diagnostic radiotion exposure in women with BRCA1 mutation or BRCA2 mutation increase risk of breast cancer (RR=1.9-3.8) [26] 9) alcohol [2,3,34,35] - increased alcohol intake by 7-14 drinks/week over 5 years [39] - folic acid may attenuate risk [34,35] - most women do not know alcohol is a risk factor [45] 10) smoking, < 18 years of age & heavy smoking (40 pack years) [21] 11) sedentary lifestyle ? [2,20] 12) postmenopausal obesity [3] - postmenopausal women with normal BMI but excess fat [41] 13) tall stature ? [3] 14) hormone replacement therapy [3,22,49] a) risk increases with duration of HRT b) risk greatest with estrogen-progestin combinations c) risk declines after cessation of HRT; returns to baseline in 3 years 15) use of oral contraceptives ? [3] 16) long-term use of calcium channel blocker associated with > 2-fold increased risk of breast cancer in postmenopausal women [31] 17) high dietary fat consumption ? [3] - low fat diet (20% fat) of no benefit (see Women's Health Initiative: Dietary Modification Trial) 18) high red meat consumption in early adulthood (RR=1.2) [36] - a combination of legumes, poultry, nuts & fish may reduce the risk of breast cancer [36] 19) upper socioeconomic class [4] 20) blacks at higher risk of breast cancer with poor prognosis [11] 21) overnight shift work/awake at night ? [5] - postulated to be due to diminished melatonin secretion 22) vitamin D deficiency [3] 23) increased breast density [3] 24) ductal hyperplasia, lobular hyperplasia 25) persistent vasomotor symptoms (RR= 1.13) [43] 26) antibiotic use? (see antibiotics & risk of breast cancer) 27) hair dyes & chemical straightener use may increase breast cancer risk [47] 28) aspirin use contoversial a) aspirin use associated with reduced risk of breast cancer [6] - odds ratio 0.8 for weekly use; 0.72 for daily use b) aspirin use associated with diminished mortality in women diagnosed with breast cancer [17] c) low dose aspirin does not reduce risk of breast cancer or breast cancer recurrence [50] 29) ibuprofen associated with reduced risk of breast cancer but association weaker than that for aspirin (which is controversial) [6] 30) caffeine consumption associated with reduced risk in women with BRCA1 or BRCA2 mutations 31) mushrooms, especially in combination with green tea reduces risk in Chinese women [14] 32) fruit intake during adolecence diminishes risk [39] 33) reduced fat, increased fruit, vegetables, & grains reduces breast cancer mortality (RR=0.82 vs usual diet) 34) bisphosphonate use associated with diminished risk (30%) [16] 35) unclear relationship of morning person vs night-owl [46] NOT risk factors: - progestin-only contraceptives [7] - high-temperature cooking methods for meat (grilling, barbecuing, pan-frying) [15] - fruit or vegetable intake in adulthood [39] Benefit/risk: - 22 high-risk women needed to be treated with tamoxifen for 5 years to prevent 1 breast cancer over 20 years [37] Radiology: - women with BRCA gene mutation should begin breast cancer screening at age 25 with MRI & mammography beginning at age 30 years - screening MRI &/or mammography at 25 years or 8 years after completion of mediastinal radiation therapy whichever comes last [3] Management: 1) women with a strong family history of breast cancer should be referred for genetic counseling [3] 2) chemoprophylaxis a) chemoprophylaxis with tamoxifen: - indications: - women age 35-60 years with breast cancer risk > 1.66% within 6 years bases on Gail model [3,8,9]* - women > 35 years of age with 5 year risk of breast cancer > 1.7% or with lobular carcinoma in situ or atypical ductal hyperplasia [3] - 20 mg QD for 5 years decreases of breast cancer by ~50% - 123 vs 224 cases, 89 vs 175 (invasive breast CA) - risk of thromboembolism increased (35 vs 22 cases) - risk of pulmonary embolus increased (18 vs 6 cases) - risk of endometrial cancer increased (36 vs 16 cases) - increased risk of cataracts [27] b) prophylaxis with raloxifene - for use after menopause (see tamoxifen for indications) - as effective as tamoxifen for reducing risk of invasive breast cancer - slightly less effective than tamoxifen for reducing risk of noninvasive breast cancer - increased risk of thromboembolism [27] c) tamoxifen & raloxifene reduce the incidence of primary hormone receptor positive invasive breast cancer by ~50% compared with placebo [3,27] - associated risk 7.0% vs 9.8% with tamoxifen over 16 years [37] - all-cause & cancer-specific mortality are not reduced [3, 27] - increased mortality with tamoxifen not statistically significant [37] - USPSTF supports recommendation for tamoxifen or raloxifene prophylaxis in high-risk postmenopausal women [32] d) prophylactic aromatase inhibitor [44] - exemestane (Aromasin) associated ~65% reduction in invasive hormone receptor- positive breast cancer in postmenopausal women at moderately increased risk [23] - anastrozole decreases risk of breast cancer in high risk women (RR=0.5 over 5 years, absolute risk reduction 2%, number needed to treat = 50) [33] 3) surgical prophylaxis a) bilateral prophylactic mastectomy - indications: - women with a family history of - multiple premenopausal breast cancer - bilateral breast cancer - BRAC1 or BRAC2 gene mutation [19] - p53 gene mutation (Li-Fraumeni syndrome) - decreases risk of breast cancer > 90% [3] b) prophylactic salpingo-oophorectectomy [6,19] - BRAC1 or BRAC2 gene mutation & have completed child-bearing - reduces risk of ovarian cancer 80% [3] 4) marine omega-3 fatty acids may be associated with lower risk of breast cancer (14%) [28] 5) weight loss & maintenance of lower weight in middle-aged women lowers risk for postmenopausal breast cancer [48] Notes: * for risk calculator (Gail Model), see [13]

Related

breast cancer screening for breast cancer

General

oncology risk factors for cancer

References

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