Maintain the T, reduce the E

Dr. Weeks’ Comment:  An aromatase inhibitor prevents one’s testosterone from metabolizing into the naturally occurring carcinogen estrogen.  Too much estrogen is toxic  –  ask your doctor to test your testosterone, your estrogen and your DHEA-S  (as well as 25-OH D3)  then, if out of balance, eat your cruciferous vegetables (BioDim) or take a prescription aromatase inhibitor.

“…Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer…”

 

Anastrozole Reduces Breast Cancer Incidence in High-Risk Postmenopausal Women

By Matthew Stenger
Posted: 3/31/2014 11:51:33 AM

  • Anastrozole significantly reduced risk of breast cancer in high-risk postmenopausal women.
  • Anastrozole was associated with significantly reduced risk of all invasive cancer, invasive estrogen receptor-positive cancer, and ductal carcinoma in situ.
  • The anastrozole group had significantly reduced risk of cancers other than breast cancer, including reduced risk of gastrointestinal and skin cancers.

In the phase III IBIS-II trial, reported in The Lancet, Cuzick et al found that aromatase inhibitor therapy with anastrozole reduced risk of breast cancer in postmenopausal women at high risk of the disease.

Study Details

In this double-blind trial, 3,864 postmenopausal women aged 40 to 70 years from 18 countries were randomly assigned between February 2003 and January 2012 to receive 1 mg of anastrozole (n = 1,920) or placebo (n = 1,944) daily for 5 years. Estimated risk for breast cancer had to be at least 2 times higher than that in the general population for women aged 45 to 60 years, at least 1.5 times higher in those aged 60 to 70 years, and 4 times higher in those aged 40 to 44 years; if patients did not meet eligibility criteria, Tyrer-Cuzick 10-year risk had to be > 5%. The primary endpoint was histologically confirmed breast cancer, consisting of invasive cancers or noninvasive ductal carcinoma in situ.

Women in the anastrozole group and placebo group were well balanced for age (median, 59.5 and 59 years), age at menarche (median, 13 years in both), age at first child birth (median, 24 years in both), body mass index (eg, < 25 kg/m2 in 30% and 29%, 25-30 kg/m2in 36% and 38%), previous use of hormone replacement therapy (47% in both, 7% and 8% within previous 12 months), hysterectomy (33% and 34%), at least two first- or second-degree relatives with breast or ovarian cancer (50% and 48%), at least one first-degree relative with breast cancer at age ≤50 years (35% and 34%), at least one first-degree relative with bilateral breast cancer (9% and 7%), lobular carcinoma in situ or atypical hyperplasia (8% and 10%), estrogen receptor-positive ductal carcinoma in situ treated with mastectomy within 6 months (8% and 9%), and 10-year Tyrer-Cuzick risk (median, 7.6% and 7.8%).

Bisphosphonates were used during the trial by 17% of patients in the anastrozole group and 15% in the placebo group.

Risk Reduction

After a median follow-up of 5 years, 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio [HR] = 0.47, < .0001). Anastrozole was associated with significantly reduced risk of all invasive cancers (2% vs 3%, HR  = 0.50, P = .001), invasive estrogen receptor-positive cancers (1% vs 2%, HR  = 0.42, P = .001), and ductal carcinoma in situ (< 1% vs 1%, HR = 0.30, P = .009), with no difference between groups in risk for invasive estrogen receptor-negative cancers (1% vs 1%, HR  = 0.79, P = .538). The predicted cumulative incidence of all breast cancers at 7 years was 5.6% vs 2.8%.

The frequency of cancers other than breast cancer was significantly lower in the anastrozole group (2% vs 4%, risk ratio [RR] = 0.58, P = .005), including lower rates of gastrointestinal cancers (RR = 0.34, P = .05) and all skin cancers (RR = 0.53, P = .05).

There were 18 deaths in the anastrozole group and 17 in the placebo group, including 2 vs 0 from breast cancer, 7 vs 10 from other cancers, 2 vs 2 from cerebrovascular accident or stroke, 3 vs 1 from cardiac arrest, and 4 vs 4 from other causes (P = .836 for differences in specific causes).

Adverse Events

There was no difference between the anastrozole and placebo groups in frequency of fractures overall (9% and 8%) or by specific sites. Similarly, there was no difference between groups in frequency of thromboembolic events (1% and 1%), cerebrovascular events (< 1% and < 1%), or myocardial infarction/cardiac failure (< 1% and < 1%).

Musculoskeletal adverse events (64% vs 58%, RR = 1.10, = .0001), including arthralgia (51% vs 46%, RR = 1.10, 95% confidence interval [CI] = 1.03-1.18), carpal tunnel syndrome (3% vs 2%, RR = 1.58, 95% CI = 1.08-2.30), and joint stiffness (7% vs 5%, RR = 1.51, 95% CI = 1.17-1.94), vasomotor symptoms (57% vs 49%, RR = 1.15, < .0001), dry eyes (4% vs 2%, RR = 1.45, 95% CI = 1.04-2.01), and hypertension (5% vs 3%, RR = 1.64, 95% CI = 1.18-2.28) were significantly more common with anastrozole. Vaginal or uterine prolapse (1% vs 2%, RR = 0.42, 95% CI = 0.22-0.81) was significantly less common with anastrozole.

The investigators concluded, “Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer.”

Jack Cuzick, PhD, of Queen Mary University of London, is the corresponding author for the The Lancet article.

The study was funded by Cancer Research UK, National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca. For full disclosures of the study authors visit www.thelancet.com.

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Dr. Weeks’ Comment:  An aromatase inhibitor prevents one’s testosterone from metabolizing into the naturally occurring carcinogen estrogen.  Too much estrogen is toxic  –  ask your doctor to test your testosterone, your estrogen and your DHEA-S  (as well as 25-OH D3)  then, if out of balance, eat your cruciferous vegetables (BioDim) or take a prescription aromatase…
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