Breast cancer: Estrogen-blocking drugs may lower the risk of death

• In a recent study, researchers ran a computer model to reassess the lifetime benefits and potential harms of estrogen-blocking drugs for breast cancer prevention in women with high risk.
• Estrogen-blocking medication coupled with yearly screening lowers the risk of invasive breast cancer and death from breast cancer by 40% and 57% respectively, but may also cause a range of mild to serious side effects.
• The benefits and harms of estrogen-blocking medication vary among individuals depending on risk factors such as age, prior biopsy, and family history of breast cancer.
• The researchers hope the study findings will facilitate decision-making about estrogen-blocking drugs in clinical practice.

According to the Centers for Disease Control and Prevention (CDC), women with a strong family history of breast cancer or inherited BRCA1 and BRCA2 gene mutations, have an increased risk of getting breast cancer.

A 2021 study concluded that women with estrogen receptor-positive (ER-positive) breast cancer are at high risk of breast cancer recurrence for up to 32 years after initial diagnosis. In ER-positive breast cancer, the tumor cells have receptors for the hormone estrogen, which fuels the growth of the tumor.

Several randomized controlled trials have shown that estrogen-blocking drugs, such as tamoxifen and exemestane (an aromatase inhibitor), could reduce the occurrence of ER-positive breast cancer by 30–50% in healthy women who are at increased risk of breast cancer.

Despite promising trial findings, the use of estrogen-blocking drugs to prevent breast cancer remains low.

According to Dr. Kathy D. Miller, professor of oncology and medicine at the Indiana University School of Medicine, this is because “many physicians and patients underestimate the benefit and overestimate the side effects.”

Now, researchers from Georgetown Lombardi Comprehensive Cancer Center and other institutions performed a computer modeling study to reassess the benefits and harms of estrogen-blocking drugs in women with a 3% or greater 5-year risk of developing breast cancer.

The results of this study were recently published in the Journal of Clinical Oncology.

A breast cancer computer model study

For the study, researchers used an existing breast cancer computer model, the Spectrum/Georgetown-Einstein (G-E) model.

The model is based on ER-positive and HER2 (human epidermal growth factor receptor 2) breast cancer data from the United States population over the period 1975–2010. It is designed to quantify the effects of screening and treatment on breast cancer incidence and mortality.

After adapting the model using data derived from meta-analyses, clinical trials, and large observational data, the researchers compared the outcomes of 5 years of estrogen-blocking medication (tamoxifen and aromatase inhibitors) coupled with annual mammography screening (with or without MRI) versus the outcomes of no medication or screening.

The results indicate the use of tamoxifen coupled with yearly screening lowered the risk of invasive breast cancer and death from breast cancer by 40% and 57% respectively when compared to no tamoxifen or screening. This equates to 95 fewer cases of invasive breast cancer and 42 fewer breast cancer deaths per 1,000 high-risk women.

Samuel Smith, Ph.D., associate professor at the University of Leeds with a research focus on improving outcomes for people living with and at risk of cancer, not involved in the study, told Medical News Today:

“This is an exciting study that carefully models the effect of preventive therapy on breast cancer incidence and death. It provides valuable information to patients and clinicians that could allow them to consider the harms and benefits of this approach. The modeling of mortality is particularly useful in the absence of long-term follow-up data of some preventive therapy trials.”

Side effects of estrogen blockers

Estrogen-blocking medications may, however, have undesirable effects.

The researchers found that tamoxifen, for instance, may result in up to 11 more endometrial cancer cases per 1,000 high-risk women.

Dr. Daniel F. Hayes, Stuart B. Padnos professor of breast cancer research at the University of Michigan Rogel Cancer Center, not involved in the study, told MNT that women who take estrogen blockers are at a higher risk for:

• immediate, but usually reversible side effects, such as hot flashes, vaginal dryness, and arthralgia (joint pain)
• possible life-threatening toxicities, such as thrombosis and uterine cancers (from tamoxifen), or osteopenia or osteoporosis and bone fracture (from aromatase inhibitors)

Dr. Ruth Heisey, associate professor at the University of Toronto and medical director of the Peter Gilgan Centre for Women’s Cancers, not involved in the study, told MNT:

“Some women may experience vaginal bleeding or discharge, mood changes, hot flashes — others tolerate [estrogen blockers] just fine.”

Benefits of estrogen-blockers for high-risk breast cancer

In the study, the researchers observed that the benefit-risk profile of these drugs could vary across individuals, and was dependent on individual risk factors such as age, prior biopsy, and family history of breast cancer.

When asked to weigh in on whether women with a high risk of ER-positive breast cancer should consider taking estrogen-blocking drugs, all experts who spoke to MNT agreed that it is up to each individual to choose what is best for them.

“The decision […] rests on a specific, personalized discussion of risks of getting cancer, benefits of reducing that risk, and risk of increased side effects and toxicities, and even secondary benefits of tamoxifen and raloxifene.”

– Dr. Daniel F. Hayes, professor of breast cancer research

Dr. Heisey said that “women should not underestimate the power of a healthy active lifestyle, reducing alcohol consumption and maintaining a healthy weight in reducing their likelihood of getting breast cancer — not a guarantee but certainly helpful.”

Those with high breast cancer risk “should be offered more intensive screening with MRI and mammogram starting at age 30, and women who want to be more proactive should discuss the opportunity of adding a risk-reducing medication with their health care provider,” Dr. Heisey added.

“For interested highest-risk women with no contraindications, I suggest after a thorough discussion of their risk-benefit profile, starting with a low dose and seeing how it goes.”

– Dr. Ruth Heisey, women’s health and cancer care expert

Dr. Heisey noted that for women with BRCA1 and BRCA2 genetic mutations, “other risk-reducing surgical options are also available.”

Next steps in breast cancer research

In their report, the researchers acknowledged that their findings are dependent on “the limitations of the data sources and the assumptions used for model development.”

The data used in this computer model study is derived from clinical trials that involved 5 years of treatment with estrogen-blocking medication, and there was limited data on the effects of shorter treatment duration in high-risk women.

Dr. Hayes pointed out that “it is not clear if the beneficial effects persist forever, or only for a certain period of time after discontinuation […] should risk reducing endocrine therapy be given for more than 5 years? Nobody knows.”

The researchers hope that “in a future study, these model results could be developed into a web-based decision tool to further facilitate shared decision making about risk-reducing drugs and mammography screening in clinical practice.”

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