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Breast Cancer

Prevention
Jose Pacheco MD

Goss et al.
Randomized, placebo-controlled, double-blind trial
Population -> post-menopausal women, at least 35 years of age or older with at least one of
the following: Age 60 years or older, Gail 5 year risk score greater than 1.66%, prior atypical
ductal or lobular hyperplasia or lobular carcinoma in situ, or DCIS with mastectomy.
N = 4560

Group 1

Exemestane
Annual incidence of invasive breast cancer -> 0.19%, HR 0.35, p = 0.002
Annual incidence of invasive + non-invasive breast cancers -> 0.35%, HR 0.47, p = 0.004
Adverse events 88%, p = 0.003

Group 2

Placebo
Annual incidence of invasive breast cancer -> 0.55%
Annual incidence of invasive + non-invasive breast cancers -> 0.77%
Adverse events 85%

Median follow-up was 35 months

ATAC group
Median follow-up period 47 months
Endpoints -> DFS, TTR, CLBC
Population -> adjuvant treatment of post-menopausal women with early stage breast cancer
Group 1
Anastrozole
Less frequent -> endometrial cancer, vaginal bleeding or discharge, cerebrovascular events, venous
thromboembolic events, hot flashes
More frequent -> musculoskeletal disorders and fractures
4 year DFS 86.9%, HR 0.86, p = 0.03
Benefit greater for those with HR positive tumors -> HR 0.82, p = 0.014

4 year TTR HR 0.83, p = 0.015


Benefit greater for those with HR positive tumors -> HR 0.78, p = 0.007

4 year CLBC recurrence -> HR 0.62, p = 0.062


Benefit greater for those with HR positive tumors -> HR 0.56, p =0.042

Group 2
Tamoxifen
4 year DFS 84.5%

Cuzick et al.
Population -> 7145 women ages 35 to 70 and at increased risk of
breast cancer
Group 1, n = 3579
Tamoxifen 20 mg/d for 5 years
Risk of invasive breast cancer HR 0.73, p = 0.004
No difference for ER negative tumors HR 1.00
Significant difference for ER positive tumors HR 0.66

RR for pulmonary embolism/DVT during active treatment 2.26


RR for pulmonary embolism/DVT after tamoxifen stopped 1.14

Group 2, n = 3575
Placebo for 5 years

Primary outcome -> incidence of breast cancer, including DCIS


Median follow-up 96 months

Fisher et al.
Population -> 13,388 women were randomly assigned to
receive placebo or tamoxifen for 5 years
Group 1

Tamoxifen
Rate of invasive breast cancer HR 0.57
Rate of non-invasive breast cancer HR 0.63
Rate of osteoporotic fractures HR 0.68

Group 2
Placebo

Fisher et al.
Population -> 13,388 women who were at increased risk for breast cancer
60 years of age or older
35-50 years of age with a 5 year predicted risk of at least 1.66%
History of lobular carcinoma in situ

Group 1, n = 6681

Tamoxifen 20 mg/d for 5 years


Risk of invasive breast cancer -> HR 0.51, p < 0.00001
Risk of non-invasive breast cancer -> HR 0.50, p < 0.002
Risk of ER positive tumors -> HR 0.31
Reduced the rate of hip fractures
Risk of endometrial cancer was increased HR 2.53 (this was mainly in those 50 years of
age and older), all were stage 1
Stroke, DVT and PE were increased (mainly in 50 years of age and up)

Group 2, n = 6706
Placebo

Median follow-up was 55 months

Vogel et al.
81 month median follow-up
Group 1
Tamoxifen 20 mg/d for 5 years

Group 2

Raloxifine 60 mg/d for 5 years


Risk for invasive breast cancer, HR 1.24 (significant)
Risk for non-invasive breast cancer, HR 1.22 (not quite significant)
Risk for endometrial cancer, HR 0.55, p = 0.003
Risk for uterine hyperplasia, HR 0.19, significant
Risk for thromboembolic events, HR 0.75, significant

Hartmann et al.
Retrospective study
Population -> women with a family history of breast cancer
who underwent prophylactic mastectomy
639 women (214 at high risk and 425 at moderate risk)
HR for breast cancer in moderate risk group -> HR 0.10, p < 0.001
HR for breast cancer in the high risk group -> HR 0.10

Control -> sisters of high risk probands who did not undergo
prophylactic mastectomy and Gail model in the patient
population
Median length of follow-up was 14 years

Domcheck et al.
Prospective, multi-center, cohort study
Population -> 2482 women who tested positive for BRCA1 or BRCA2
Risk reducing mastectomy
N = 257
No breast cancers diagnosed in this population (compared to 7% without)

Risk reducing salping-oopherectomy


N = 993
1.1% diagnosed with ovarian cancer (5.8% without)

In those with a history of breast cancer, HR 0.31


In those without a history of breast cancer, HR 0.15
Lower risk of first breast cancer in BRCA1 mutation carriers, HR 0.63
Lower risk of first breast cancer in BRCA2 mutation carriers, HR 0.36
All cause mortality, HR 0.40
Breast cancer specific mortality, HR 0.44
Ovarian cancer specific mortality, HR 0.25

11.4% with breast cancer (19.2% without)


3.4% died from any cause (10% without)

Outcomes -> breast and ovarian cancer risk, cancer specific and overall mortality

Domcheck et al.