Breast Cancer Prevention: Comparing Tamoxifen and Aromatase Inhibitors

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• Tamoxifen vs Anastrozole Overview
• Menopausal Status and Treatment Selection
• Tamoxifen Side Effects and Risks
• Risk-Benefit Analysis for Patients
• Long-Term Protection and Utilization
• Full Transcript

Tamoxifen vs Anastrozole Overview

Dr. Marc Lippman, MD, provides a clear comparison between Tamoxifen and aromatase inhibitors like anastrozole for breast cancer chemoprevention. Tamoxifen is the more widely recognized medication, having been used for decades. Aromatase inhibitors represent a more modern approach to reducing breast cancer risk in appropriate patient populations.

Dr. Anton Titov, MD, explores these treatment options with Dr. Lippman to understand their respective roles in clinical practice. The choice between these medications depends heavily on patient-specific factors and menopausal status.

Menopausal Status and Treatment Selection

Menopausal status is the critical factor determining appropriate breast cancer prevention therapy. Dr. Marc Lippman, MD, explains that aromatase inhibitors cannot be used in premenopausal women due to their functioning ovaries. When estrogen concentrations decrease from an aromatase inhibitor, gonadotrophins increase and stimulate the ovaries to produce more estrogen, effectively overcoming the medication's block.

This mechanism only works effectively in postmenopausal women whose ovaries no longer function. Dr. Marc Lippman, MD, notes that while premenopausal breast cancer is tragic, the overwhelming majority of breast cancers occur in postmenopausal women, with a median age of diagnosis at 56 years.

Tamoxifen Side Effects and Risks

Dr. Marc Lippman, MD, addresses the specific side effect profile of Tamoxifen that concerns both patients and physicians. The medication carries a risk of thrombosis and occasionally pulmonary embolus, which are serious side effects requiring careful consideration. Proper patient screening can identify those with previous thrombotic histories, obesity, or inactivity, allowing for safer Tamoxifen use.

Additionally, approximately one woman in 150 who takes Tamoxifen for five years will develop low-grade endometrial cancer. Dr. Marc Lippman, MD, emphasizes that this cancer is typically readily treated by hysterectomy, but the risk understandably causes concern among patients considering chemoprevention.

Risk-Benefit Analysis for Patients

Dr. Marc Lippman, MD, provides crucial context for understanding the risk-benefit ratio of breast cancer chemoprevention. Tamoxifen reduces the risk of lethal breast cancer by 50%, which must be weighed against the smaller risk of endometrial cancer. This risk-benefit calculation favors treatment for most appropriate candidates, though Dr. Lippman acknowledges that patients often struggle with this type of statistical thinking.

Dr. Anton Titov, MD, discusses with Dr. Lippman the logical approach of waiting until postmenopause to use more effective aromatase inhibitors. This strategy would prevent most breast cancers while avoiding the specific risks associated with Tamoxifen in premenopausal women.

Long-Term Protection and Utilization

The protective effects of Tamoxifen demonstrate remarkable longevity according to Dr. Marc Lippman, MD. Two massive clinical trials involving over 10,000 patients proved Tamoxifen's efficacy as a chemoprevention agent. The protection from just five years of Tamoxifen use persists for many years afterward, providing sustained risk reduction.

Despite this proven efficacy, Dr. Marc Lippman, MD, notes that aromatase inhibitors are not widely used for breast cancer prevention. He considers this particularly unfortunate given that breast cancer remains the most common malignancy in women. Even non-invasive breast cancer carries substantial morbidity, making effective prevention strategies critically important.

Full Transcript

Dr. Anton Titov, MD: Tamoxifen is more widely known than the aromatase inhibitors such as anastrozole. Is anastrozole a more modern medication for chemoprevention of breast cancer? How should the consideration be given?

Dr. Marc Lippman, MD: First of all, aromatase inhibitors really can't be used in premenopausal women. But the overwhelming majority of breast cancers are in postmenopausal women, so that's not a huge problem.

You can't use aromatase inhibitors in premenopausal women because you have functioning ovaries. If you reduce estrogen concentrations with an aromatase inhibitor, gonadotrophins go up. Then you stimulate a functional ovary, and you make more estrogen, so you overcome the block.

You can't do that in a postmenopausal woman because her ovaries don't work anymore. So her rising gonadotropins don't increase your estrogen concentrations. Aromatase inhibitors are primarily used in postmenopausal women.

Now, Tamoxifen does rarely have some toxicities that are worrisome—thrombosis and occasionally pulmonary embolus. That's a serious side effect; no question about it.

But if you screen patients to find those who have had previous histories of thrombi, who are inactive, who have obesity, you can use Tamoxifen reasonably safely.

One woman in 150 who takes Tamoxifen for five years will develop low-grade endometrial cancer, readily treated by hysterectomy. If you're a normal person and you don't have any risks at all, and someone tells you a drug might cause endometrial cancer, you might say you'll have nothing to do with it.

But of course, that has a risk-benefit ratio. If you can reduce your risk of a lethal disease—breast cancer—by 50%, you run half of the endometrial cancer. Obviously, if you're playing the odds, it's what you would do here.

But most people don't play odds like that correctly. They just get afraid and don't do things.

So for postmenopausal women, it's Tamoxifen versus anastrozole at this point. For premenopausal women, Tamoxifen does work as a chemoprevention agent that was proven in two huge studies involving, as I said, north of 10,000 patients.

The risk of breast cancer is much lower in women under the age of 50 than we think. Tragically, it's a premenopausal breast cancer. The median age of breast cancer is 56 years of age; most patients are postmenopausal.

But there are remarkable benefits in these prevention clinical trials, which had been followed up for many years. Five years taking Tamoxifen, the protection persists for so in many cases, you might say this.

Why don't we wait till women are postmenopausal and then give them an aromatase inhibitor, which is more effective? You are going to be preventing most breast cancer. And that makes sense to me too; I would take half a loaf here.

These aromatase inhibitors just aren't widely used to prevent breast cancer. And it's very unfortunate because breast cancer is still the most common malignancy of women overwhelmingly, and then the morbidities associated even with non-invasive breast cancer are substantial.