Anti-Estrogen Medication for Breast Cancer

(MAPPER Trial)

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Must be taking: Anti-estrogen

Must not be taking: Strong CYP2D6 inhibitors

Disqualifiers: T4, N1-3, M1 cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests anti-estrogen medications, such as aromatase inhibitors and Tamoxifen, to evaluate their effectiveness when started before surgery in treating breast cancer. The focus is on women with specific types of breast cancer that are positive for estrogen or progesterone receptors, indicating that the cancer cells grow in response to these hormones. It targets women diagnosed with early-stage invasive breast cancer, with no signs of the cancer spreading to lymph nodes or other parts of the body. Participants should have undergone a recent breast exam and imaging tests and must not have received prior treatment for this cancer. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does prohibit strong CYP2D6 inhibitors if you are taking tamoxifen, as they can reduce its effectiveness. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that both aromatase inhibitors and tamoxifen are well-researched treatments for breast cancer. Aromatase inhibitors can extend life and lower the chances of cancer recurrence. They also reduce the risk of dying from breast cancer. Tamoxifen has served as a standard treatment for many years. Both treatments are effective, but they can cause side effects like hot flashes or joint pain. However, most patients tolerate these treatments well. Prospective trial participants should note that many breast cancer patients already use these medications safely. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about aromatase inhibitors and tamoxifen because they offer a targeted approach to treating breast cancer by focusing on hormone regulation. Unlike chemotherapy, which attacks rapidly dividing cells indiscriminately, these treatments specifically block estrogen production or its effects, which can fuel the growth of certain breast cancers. Aromatase inhibitors work by lowering estrogen levels in the body, while tamoxifen blocks estrogen receptors on cancer cells. This specificity not only helps in effectively slowing down the cancer's progression but also tends to result in fewer side effects compared to broader treatments like chemotherapy.

What evidence suggests that this treatment might be an effective treatment for breast cancer?

Studies have shown that aromatase inhibitors, which participants in this trial may receive as part of the standard-of-care endocrine therapy, effectively treat hormone-sensitive breast cancer, especially in postmenopausal women. These medications lower estrogen levels, helping to slow or stop the growth of certain breast cancers. Research indicates that taking aromatase inhibitors for five years can reduce the risk of dying from breast cancer by about 40% over ten years, compared to using tamoxifen for the same period. Tamoxifen, also part of the standard-of-care endocrine therapy in this trial, is another effective treatment option. However, it is generally less effective unless combined with ovarian suppression treatments in premenopausal women. Overall, evidence strongly supports these treatments for significantly improving survival rates in the appropriate patient groups. ^{1 2 6 7 8}

Who Is on the Research Team?

Lubna N. Chaudhary

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

This trial is for individuals with hormone receptor-positive, HER2-negative breast cancer. Participants will receive standard anti-estrogen treatment before surgery for about 4 to 12 weeks. Specific eligibility details are not provided.

Inclusion Criteria

I haven't been treated for any cancer in the past 2 years, except for non-dangerous skin cancer or early-stage cervical cancer.

I am using or willing to use non-hormonal birth control methods.

I am not taking strong CYP2D6 inhibitors with tamoxifen.

Exclusion Criteria

Pregnant or lactating women are ineligible

Medical, psychiatric or other condition that would prevent the patient from receiving the protocol therapy or providing informed consent

I am a man with breast cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Endocrine Treatment

Participants receive standard-of-care anti-estrogen treatment preoperatively

4-12 weeks

Surgery

Surgical resection of breast tumors

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aromatase Inhibitors/Tamoxifen

Trial Overview The study tests how effective aromatase inhibitors or tamoxifen are when given as a short-term neoadjuvant (pre-surgery) endocrine treatment in patients with certain types of breast cancer.

How Is the Trial Designed?

Group I: Standard-of-care Endocrine therapy Experimental Treatment 1 Intervention

Once enrolled, patients would be treated with the current standard-of-care endocrine therapy.

Aromatase Inhibitors/Tamoxifen is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Tamoxifen for:

• Hormone receptor-positive breast cancer
• Prevention of breast cancer in high-risk individuals

Approved in United States as Tamoxifen for:

• Hormone receptor-positive breast cancer
• Ductal carcinoma in situ (DCIS)
• Prevention of breast cancer in high-risk individuals

Approved in European Union as Aromatase Inhibitors (e.g., Anastrozole, Letrozole, Exemestane) for:

• Hormone receptor-positive breast cancer in postmenopausal women
• Advanced breast cancer in postmenopausal women

Approved in United States as Aromatase Inhibitors (e.g., Anastrozole, Letrozole, Exemestane) for:

• Hormone receptor-positive breast cancer in postmenopausal women
• Advanced breast cancer in postmenopausal women

Approved in Canada as Tamoxifen/Aromatase Inhibitors for:

• Hormone receptor-positive breast cancer
• Prevention of breast cancer in high-risk individuals

Approved in Japan as Tamoxifen/Aromatase Inhibitors for:

• Hormone receptor-positive breast cancer

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

In a study using a breast tumor model with ovariectomized mice, letrozole was found to significantly extend the time for tumor progression compared to tamoxifen alone or in combination with letrozole, with letrozole alone allowing tumors to double in size after 34 weeks versus 16 weeks for tamoxifen.

Tumors that progressed while on tamoxifen remained sensitive to second-line treatment with letrozole, indicating a potential treatment pathway, while tumors progressing on letrozole did not respond to subsequent antiestrogen therapies, highlighting the need for further research on effective second-line options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic strategies using the aromatase inhibitor letrozole and tamoxifen in a breast cancer model. Long, BJ., Jelovac, D., Handratta, V., et al.[2022]

Letrozole is a new non-steroidal aromatase inhibitor approved in Japan for treating postmenopausal women with breast cancer, particularly effective for those with steroid receptor positive or receptor-unknown locally advanced or metastatic cases.

The drug is generally well-tolerated, with mostly mild side effects such as hot flashes and fatigue, and has shown beneficial results in large international studies for post-surgical endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Introduction of new drug: letrozole, a new non-steroidal aromatase inhibitor for the treatment of postmenopausal women with breast cancer]. Tsukagoshi, S.[2018]

The ATAC trial, involving over 9,000 postmenopausal women, demonstrated that anastrozole significantly improves disease-free survival and reduces recurrence rates compared to tamoxifen, with benefits continuing even after treatment ends.

Anastrozole also has a favorable safety profile compared to tamoxifen, suggesting it may be a better initial treatment option for early breast cancer, especially when considering long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole as an adjuvant endocrine treatment for postmenopausal patients with breast cancer: emerging data. Buzdar, AU., Cuzick, J.[2018]

Aromatase inhibitors like exemestane, letrozole, and anastrozole may be more effective than tamoxifen in preventing breast cancer recurrence, with ongoing studies to confirm their efficacy in the adjuvant setting.

These aromatase inhibitors have tolerability profiles that are similar to or better than tamoxifen, making them suitable alternatives for patients who cannot tolerate standard tamoxifen therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiaromatase agents: evolving role in adjuvant therapy. Jones, SE.[2018]

Aromatase inhibitors like anastrozole, letrozole, and exemestane are now the preferred hormonal treatments for estrogen-receptor-positive, postmenopausal metastatic breast cancer, replacing older therapies such as tamoxifen.

Recent studies have confirmed the effectiveness of these aromatase inhibitors in managing breast cancer, highlighting their critical role in targeting the hormonal pathways involved in the disease's progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonsteroidal and steroidal aromatase inhibitors in breast cancer. Hamilton, A., Volm, M.[2018]

Aromatase inhibitors, like anastrozole, are effective and have low toxicity, making them a standard treatment for hormone-responsive metastatic breast cancer, and they are being evaluated for use in early breast cancer as adjuvant therapy.

While initial results for aromatase inhibitors in early breast cancer are promising, it is still too early to recommend their routine use in this setting, although anastrozole is a suitable option for patients who cannot take tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors as adjuvant therapy in breast cancer. Visvanathan, K., Davidson, NE.[2018]

Aromatase inhibitors like anastrozole and letrozole significantly alter gene expression in estrogen receptor positive breast cancer, affecting both classical estrogen-dependent genes and other genes related to tumor proliferation and extracellular matrix remodeling.

The study, involving 34 patients treated for 2 weeks before surgery, found no significant differences in molecular effects between the two drugs, suggesting they have similar mechanisms of action in suppressing estrogen synthesis and altering tumor biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular response to aromatase inhibitor treatment in primary breast cancer. Mackay, A., Urruticoechea, A., Dixon, JM., et al.[2022]

Anastrozole and letrozole have been shown to be equivalent or superior to tamoxifen in treating women with metastatic breast cancer, based on large Phase III trials, indicating their effectiveness as first-line therapies.

In the adjuvant setting, early results from the ATAC trial suggest that anastrozole may provide a small but statistically significant improvement in disease-free survival compared to tamoxifen, although more follow-up is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical differences among the aromatase inhibitors. Ligibel, JA., Winer, EP.[2007]

Anastrozole and letrozole are effective oral treatments for advanced breast cancer in postmenopausal women, especially when other therapies like tamoxifen have not worked.

Both drugs are claimed to be more effective and less toxic than the standard treatment, megestrol acetate, although the review assesses the validity of these claims.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New aromatase inhibitors for breast cancer. [2019]

A pooled analysis of 9 clinical trials involving 3908 patients found that aromatase inhibitors (AIs) do not significantly improve overall response rate (ORR) or time to disease progression (TTP) compared to megestrol acetate (MEG) in treating metastatic breast carcinoma.

While AIs caused more hot flashes, they resulted in less weight gain, dyspnea, and peripheral edema compared to MEG, indicating a different toxicity profile that may influence treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New aromatase inhibitors as second-line endocrine therapy in postmenopausal patients with metastatic breast carcinoma: a pooled analysis of the randomized trials. Carlini, P., Bria, E., Giannarelli, D., et al.[2018]

In a study involving 6182 postmenopausal women with hormone-receptor-positive breast cancer, sequential treatment with tamoxifen and letrozole did not significantly improve disease-free survival compared to letrozole monotherapy, indicating that letrozole alone may be sufficient for treatment.

The updated analysis showed no statistically significant difference in overall survival between letrozole and tamoxifen monotherapy, suggesting that both treatments have similar long-term outcomes, with adverse events consistent with previous reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. Mouridsen, H., Giobbie-Hurder, A., Goldhirsch, A., et al.[2022]

Letrozole, a nonsteroidal aromatase inhibitor, has been found to be superior to tamoxifen in treating metastatic breast cancer, indicating its potential to replace tamoxifen in various treatment scenarios.

The review highlights the need for further clinical studies to compare the risks and benefits of letrozole and tamoxifen for new indications, particularly in adjuvant therapy for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole in the treatment of breast cancer. Shaw, HS., Ellis, MJ.[2019]

In a study involving 3697 postmenopausal women with hormone receptor-positive early breast cancer, the upfront treatment with aromatase inhibitors for 5 years did not show superior disease-free survival compared to a switch strategy of 2 years of tamoxifen followed by 3 years of aromatase inhibitors, with 5-year disease-free survival rates of 89.8% and 88.5%, respectively.

No significant differences in efficacy were found among the three aromatase inhibitors (anastrozole, exemestane, and letrozole), suggesting that factors like patient preference and tolerability should guide treatment decisions rather than efficacy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial. De Placido, S., Gallo, C., De Laurentiis, M., et al.[2019]

Citations

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Aromatase Inhibitors - StatPearls - NCBI Bookshelf Aromatase inhibitors (AIs) are indicated in the treatment of hormone-receptive breast cancer in postmenopausal women in various settings.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0140673615610741

Aromatase inhibitors versus tamoxifen in early breast cancer 5 years of an aromatase inhibitor reduces 10-year breast cancer mortality rates by about 15% compared with 5 years of tamoxifen, hence by about 40% ( ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35123662/

Aromatase inhibitors versus tamoxifen in premenopausal ... Aromatase inhibitors are more effective than tamoxifen in postmenopausal women but are ineffective in premenopausal women when used without ovarian suppression.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2104162

Duration of Adjuvant Aromatase-Inhibitor Therapy in ... Taking these results together, we concluded that there was no firm evidence of a benefit for prolonged aromatase-inhibitor therapy in ...

5. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)01013-X/fulltext

Extending the duration of endocrine treatment for early ... We conducted individual patient data meta-analyses of 12 randomised trials, including 22 031 women who had completed at least 5 years of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3846460/

Aromatase inhibitors in the treatment of breast cancer ... Aromatase inhibitors have shown incremental improvements in disease-free survival, lower local recurrence rates, lower metastatic recurrence rates, and a lower ...

7. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044750

Aromatase Inhibitors and the Risk of Cardiovascular ... These drugs have been associated with favorable clinical outcomes, including decreased risks of all-cause and breast cancer–related mortality, ...

8. cancer.org cancer.org/cancer/types/breast-cancer/risk-and-prevention/aromatase-inhibitors-for-lowering-breast-cancer-risk.html

Breast Cancer Prevention: Aromatase Inhibitors In large studies, both anastrozole and exemestane have been shown to lower breast cancer risk in postmenopausal women who are at increased risk.