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Hi Opale:

Are you asking about trials of Aromatase Inhibitors ("AI") in the adjuvant setting of early stage invasive breast cancer?

Studies evaluating an initial five years of an AI-containing regimen in the adjuvant setting of early stage invasive breast cancer are of two main types:

(1) 5-year "Monotherapy" regimens of an AI versus Tamoxifen ("Tam")

(2) 5-year "Switch" regimens (e.g., 2 yrs Tam followed by 3 yrs AI) versus 5 yrs Tam

To my knowledge, the various studies (e.g., ATAC, BIG 1-98, etc.) did not compare an AI to no endocrine therapy. They compared new AIs to other endocrine therapy regimens (e.g., 5 yrs Tam).

Accordingly, the study publications reported the modest advantages achieved by certain AI-containing regimens over other regimens (e.g., 5 yrs Tam). (Head-to-head studies of various AIs were also undertaken.)

The absolute risk reduction benefit of AI monotherapy versus no endocrine therapy would be expected to be substantially larger than the absolute benefit shown over Tam in such studies.

The benefits of Tamoxifen versus no treatment can be substantial. One cannot properly compare across studies for various reasons, such as differences between study populations. However, for some information about the absolute benefits of Tamoxifen in reducing recurrence risk and mortality in early stage invasive breast cancer, see this meta analysis:

EBCTCG, Davies (2011): "Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials"

Main Page (with Supplemental materials) : http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60993-8/abstract

PDF version: http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(11)60993-8.pdf

Importantly, it is well-established that the benefits of endocrine therapy are proportional to recurrence risk. For example, the above states: "Hence, the absolute risk reductions produced by tamoxifen depend on the absolute breast cancer risks (after any chemotherapy) without tamoxifen."

This means that those at greater residual risk after all other treatments potentially reap larger absolute benefits than those with lower residual risk.

To your question, the relative risk reduction benefit of AIs as initial monotherapy in early stage invasive breast cancer versus no endocrine therapy is often given as ~ 50%. Please confirm it with your medical oncologist.

Example 1: If residual recurrence risk after all other treatments is 28%, a relative risk reduction of 50% translates to an absolute risk reduction benefit of 14%, versus no endocrine therapy. (28 x 0.50 = 14%)

Example 2: If the residual risk is 18%, a relative risk reduction of 50% translates to an absolute risk reduction benefit of 9%, versus no endocrine therapy. (18 x 0.50 = 9%)

Because potential benefit is proportional to risk, patients should seek current, case-specific advice from their medical oncologist regarding their estimated recurrence risk after all other treatments, the potential relative risk reduction benefit and estimated absolute benefit of any proposed endocrine therapy regimen in their case. This in turn is weighed against the risks of such treatment.

Endocrine therapy can reduce the risks of distant (metastatic) recurrence, as well as loco-regional recurrence or new disease (e.g., contralateral breast cancer). So be sure to ask about the type of any risk estimates provided to you by your medical oncologist. For example, what type of recurrence risk is being discussed? (5-year? 10-year? Distant? Other?)

Please review any information or materials from outside sources with your medical oncologist to confirm accurate understanding, as well as currency and applicability to your case.

BarredOwl

[Edit: Please note that Opale did not have any profile information displayed at the time of this reply, which emphasized that the information applies to initial adjuvant endocrine therapy in early stage invasive breast cancer. Different studies pertain to her situation of Stage IIIB disease, illustrating why is it important to seek case-specific advice and to confirm the individual applicability of any outside information with your MO.]

By the way, I would be quite surprised if, in the setting of early stage invasive breast cancer, in a trial including patients with any significant distant recurrence risk, you could find a trial of an AI versus placebo as INITIAL therapy in the first five years. This is because clinical trials are subject to ethical constraints, and new drugs are compared with treatments representing then current standard of care, and not to placebo.

The case of extended therapy was different, because extended treatment was not part of the standard of care. The standard of care would have been 5 years of Tamoxifen with no additional therapy after 5 years. Therefore, in an extended therapy trial, an arm in which patients received placebo after having received 5-years of Tamoxifen was acceptable.

BarredOwl