Breast Cancer Chemoprevention: Medications to Reduce Your Risk

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• What is Breast Cancer Chemoprevention?
• Tamoxifen for Breast Cancer Prevention
• Aromatase Inhibitors for Prevention
• Comparing Prevention Medications
• Who is a Candidate for Chemoprevention?
• Future of Breast Cancer Prevention

What is Breast Cancer Chemoprevention?

Breast cancer chemoprevention is the use of pharmaceutical medications to reduce the risk of developing the disease. As Dr. Jack Cuzick, MD, explains, this field has advanced significantly through clinical trials, offering a powerful strategy for women at high risk. The concept was initially proven by observing that drugs used to treat existing breast cancer also prevented new cancers from forming in the opposite breast.

This approach is particularly important because breast cancer remains the most common cancer in women globally. Chemoprevention provides a proactive option beyond lifestyle changes for those with a heightened genetic or clinical risk profile.

Tamoxifen for Breast Cancer Prevention

Tamoxifen was the pioneering medication in breast cancer chemoprevention. Dr. Jack Cuzick, MD, notes that its preventive effects were first observed as early as 1985 in women being treated for cancer in one breast. Researchers saw that these patients experienced a 50% reduction in new tumors developing in the contralateral, or opposite, breast.

Subsequent dedicated prevention clinical trials confirmed that tamoxifen provides about a 50% reduction in estrogen receptor-positive breast cancers specifically. However, it has no real impact on estrogen receptor-negative cancers, leading to an overall breast cancer risk reduction of approximately 35%. This foundational work established the viability of chemoprevention as a clinical strategy.

Aromatase Inhibitors for Prevention

For postmenopausal women, aromatase inhibitors represent a more recent and potent advancement in breast cancer chemoprevention. Dr. Jack Cuzick, MD, highlights that medications like anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) were first proven to be more effective than tamoxifen in treating active breast cancer. Analysis of these treatment trials showed they also had a bigger preventive effect on new contralateral breast tumors.

This evidence led to clinical trials specifically for cancer prevention. The results are striking, with Dr. Cuzick reporting that aromatase inhibitors demonstrate a 50% to 70% reduction in breast cancer recurrence and primary prevention for estrogen receptor-positive cancers. This represents a significant improvement in preventive efficacy for the appropriate patient population.

Comparing Prevention Medications

Direct head-to-head clinical trials comparing tamoxifen versus anastrozole for primary prevention would be enormous and are unlikely to be conducted. However, Dr. Jack Cuzick, MD, explains that clear indirect evidence from treatment trials and contralateral tumor data strongly suggests that anastrozole is probably more effective for prevention in postmenopausal women.

The key difference lies in their mechanisms and patient suitability. Tamoxifen can be used in both premenopausal and postmenopausal women, while aromatase inhibitors are only for postmenopausal women. Both classes of drugs specifically target and prevent estrogen receptor-positive breast cancers, which comprise a majority of cases.

Who is a Candidate for Chemoprevention?

Chemoprevention is not for everyone; it is targeted at women with a high risk of developing breast cancer. Dr. Jack Cuzick, MD, mentions that guidelines, such as those from the NICE committee in the UK, already recommend tamoxifen and raloxifene for prevention in high-risk women. This decision is based on a careful assessment of an individual's personal and family history, genetic markers like BRCA mutations, and other risk factors.

The potential addition of aromatase inhibitors to these guidelines is currently under review. Dr. Cuzick is hopeful that anastrozole will be added to the prevention armamentarium, offering a more effective option for eligible postmenopausal women at high risk.

Future of Breast Cancer Prevention

The field of breast cancer chemoprevention continues to evolve rapidly. As Dr. Jack Cuzick, MD, indicates, committees are actively reviewing the robust new data on aromatase inhibitors to consider formal recommendations for their use in prevention. The evidence is very strong, and their adoption would mark a significant step forward.

Ongoing clinical trials will provide even more data, potentially refining which subgroups of high-risk women benefit most from which medication. The goal is to expand the arsenal of preventive options, making personalized, effective risk reduction accessible to more women. The work of experts like Dr. Cuzick is crucial in turning clinical research into life-saving public health recommendations.

Full Transcript

Dr. Anton Titov, MD: Chemoprevention of cancer is an important area. Chemoprevention means the use of pharmaceuticals in cancer prevention. Breast cancer is the most common cancer in women. There are some strategies for chemoprevention of breast cancer.

You have done seminal work in this cancer prevention area. The results from clinical trials demonstrate chemoprevention of breast cancer is very effective. What are the strategies to prevent breast cancer by medications?

Dr. Jack Cuzick, MD: I think breast cancer is one of these unique examples. We have learned a lot about treating breast cancer with hormonal therapies. You are treating cancer arising in one breast, then you can observe in that same woman whether new cancer arises in the opposite side, in another breast.

This was originally done for tamoxifen. I think it was as early as 1985. Then we reported preventive effects of tamoxifen in the early clinical trials. Tamoxifen use to treat breast cancer was producing 50% reductions in contralateral tumors.

Now that's held up in terms of estrogen receptor-positive cancers. In the prevention clinical trials, you get about 50% reduction of breast cancer in contralateral breast. But there's no real impact of tamoxifen on estrogen receptor-negative cancer. So the overall benefit of tamoxifen is about 35% reduction of breast cancer.

More recently, for postmenopausal breast cancer, new cancer-preventing medications appeared. The aromatase inhibitors have been shown to be more effective than tamoxifen in therapy of breast cancer: anastrozole (Arimidex), letrozole (Femara), exemestane (Aromasin). They prevent recurrence and deaths from breast cancer.

In those clinical trials, we have been able to look at new contralateral breast tumors. We have seen bigger preventive effect on contralateral breast tumors with the aromatase inhibitors than with tamoxifen. Aromatase inhibitors are anastrozole, letrozole or exemestane.

So this led us and others to do clinical trials of aromatase inhibitors for cancer prevention only in postmenopausal women. Yes, the cancer-preventive effect sizes are larger than you see for tamoxifen. Anastrozole (Arimidex), letrozole (Femara), exemestane (Aromasin) have breast cancer-preventive effects on the order of 50% to 70% reduction in cancer recurrence.

Dr. Anton Titov, MD: In primary prevention? In primary prevention of breast cancer.

Dr. Jack Cuzick, MD: Again, the preventive effects are only on estrogen receptor-positive cancers. But the cancer-preventing effects of aromatase inhibitors are really quite striking. So we're quite excited about that.

There have been no direct prevention clinical trials comparing tamoxifen vs anastrozole. Those clinical trials will have to be enormous to get a clear answer. But we are getting clear indirect answers that anastrozole is probably more effective.

We are also seeing that supported by contralateral breast tumors in the breast cancer treatment clinical trials. There are clinical trials ongoing, and more data coming in. It is there a potential recommendation for postmenopausal women to take aromatase inhibitors. It will happen maybe sometime in the future.

Dr. Anton Titov, MD: Anastrozole (Arimidex), letrozole (Femara), exemestane (Aromasin) work for certain subgroups of women perhaps? My expectation is that there will be recommendation to use aromatase inhibitors for breast cancer prevention.

The NICE committee in the UK has now recommended tamoxifen and raloxifene for prevention of breast cancer in high-risk women.

Dr. Jack Cuzick, MD: Those recommendations were made before aromatase inhibitor prevention data were available. The committees are currently meeting right to consider whether they should recommend aromatase inhibitors for breast cancer prevention.

Dr. Anton Titov, MD: These medications are anastrozole, letrozole or exemestane. I think the evidence is very strong. I would be hopeful that anastrozole would be added to the armamentarium of what we can do to prevent breast cancer: anastrozole (Arimidex), letrozole (Femara), exemestane (Aromasin).