Risk reduction stats

Opale

Does anyone have good source of reliable stats on what the percentage reduction in recurrence risk is with and without AI (such as letrozole)? I heard that the risk reduction is 50% (based on 6% recurrence rate without use of AI and compared to 3% with use of AI drugs). Can anyone confirm or give me direction to the stats?

BarredOwl

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.]

Opale

Thanks BarredOwl that's exactly what I was seeking (luckily I have a Harvard medical school post-doctoral grad in my family to make sure I understand the details) Yes, I'll ask my oncologist about my specific risk of recurrence when I meet with her later this month. I like to have some knowledge under my belt so I can have a meaningful discussion with my doctors. Your post was simply awesome! Best, Opale

Opale

Thanks KB870, I'll look at that information as well although I'm always have some healthy skepticism about studies from pharmaceutical manufacturers. Ever ask a pharmaceutical inventor what drugs they take? I have. The answer so far is none. Makes you wonder what they know that we don't. Thanks so much! Opale

BarredOwl

Hi KB870:

My post above expressly concerns studies of "INITIAL" adjuvant therapy in the first five years, because that is what is relevant to those newly diagnosed and considering "initial" adjuvant endocrine therapy for early stage invasive disease.

The trial you mentioned is NOT a trial of 5 years AI versus placebo as "initial" up-front treatment in years 1 to 5.

The trial described in Section 14.2 is a completely different type of "EXTENDED" therapy trial that concerns extending therapy beyond the initial 5 years of treatment:

14.2 Extended Adjuvant Treatment of Early Breast Cancer, Median Treatment Duration of 24 Months

A double-blind, randomized, placebo-controlled trial of Femara was performed in over 5,100 postmenopausal women with receptor-positive or unknown primary breast cancer who were disease free after 5 years of adjuvant treatment with tamoxifen."

According to the content you cited, the patients in that trial all received 5 years of adjuvant tamoxifen.

Then, after 5-years of Tamoxifen, they were randomized to receive either an AI or placebo for an additional five years, although due to favorable results, the trial was terminated early.

I note that numerous other clinical trials have been completed since that one that add to our understanding of the potential benefits of extending endocrine therapy beyond 5 years. Patients who have already received 5-years of endocrine therapy and are considering continuing or "extending" treatment in years 6 through 10, should seek current, case-specific medical advice from their medical oncologist regarding the potential benefit of extended therapy in their specific case.

BarredOwl

BarredOwl

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

Falconer

Barred Owl- I always read your posts with reverence. Thank you for keeping track of all of us. I often feel like Inigo Montoya does in the following:

I am certain you are not "no one of consequence". Thank you again for looking out for us all.