Hormone Therapy for Male Breast Cancer
Recruiting in Palo Alto (17 mi)
+7 other locations
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Jose Pablo Leone
Disqualifiers: Inflammatory breast cancer, severe cardiac disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This research study is looking to see how well male breast cancer responds to preoperative treatment with endocrine therapy and which endocrine therapy regimen is the most effective treatment for male breast cancer.
The drugs used in this study are:
* Tamoxifen
* Anastrozole
* Degarelix
* Abemaciclib
Do I need to stop my current medications to join the trial?
The trial information does not specify whether you need to stop taking your current medications. However, if you have been on any endocrine therapy, chemotherapy, or radiation therapy for breast cancer or any other cancer in the past 12 months, you would not be eligible to participate.
What data supports the effectiveness of the drug Abemaciclib, Verzenio, LY2835219, Ramiven, Abemaciclib, Anastrozole, Arimidex, Degarelix, Firmagon, Tamoxifen, Nolvadex, Tamoxifen citrate for male breast cancer?
Hormone therapy, including drugs like Tamoxifen, is commonly used for male breast cancer due to the high rate of hormone receptor positivity in these tumors. Although specific data on newer drugs like Abemaciclib and Anastrozole in male breast cancer is limited, they are used based on their effectiveness in female breast cancer, which shares similar hormone receptor characteristics.
12345Is hormone therapy for male breast cancer generally safe?
Tamoxifen, a common hormone therapy for male breast cancer, is associated with a high rate of treatment-limiting symptoms. Anastrozole, another hormone therapy, has been used without adverse events in some cases, but more research is needed to fully understand its safety in men.
678910How does the drug combination of Abemaciclib, Anastrozole, Degarelix, and Tamoxifen differ from other treatments for male breast cancer?
This drug combination is unique because it includes Abemaciclib, a newer drug that targets specific proteins involved in cell division, alongside traditional hormone therapies like Tamoxifen and Anastrozole, which are commonly used in female breast cancer but less studied in males. This approach may offer a novel way to address the hormone receptor-positive nature of most male breast cancers.
1461112Eligibility Criteria
This trial is for men aged 18+ with invasive breast cancer that's hormone receptor-positive and HER2-negative, who haven't had surgery yet. Participants must be able to take oral meds, have certain organ function levels, and use contraception if with a partner of childbearing potential. Excluded are those with serious medical conditions, active infections, inflammatory breast cancer or recent treatments for other cancers.Inclusion Criteria
I can take pills by mouth.
I am willing to have a breast biopsy after the initial treatment phase.
I have had ductal or lobular carcinoma in situ in either breast.
+9 more
Exclusion Criteria
The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study
I currently have an active infection (bacterial, fungal, or viral).
I have been diagnosed with inflammatory breast cancer.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Window Phase
Participants receive endocrine therapy for 3 weeks to evaluate initial response
3 weeks
1 visit (in-person)
Treatment
Participants receive one of four endocrine therapy treatment combinations for 4 months
4 months
4 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
6 months
2 visits (in-person)
Long-term Follow-up
Participants are followed for up to 10 years to monitor long-term outcomes
10 years
Participant Groups
The ETHAN study tests how male breast cancer responds to preoperative endocrine therapy. It compares the effectiveness of Tamoxifen, Anastrozole, Degarelix, and Abemaciclib in treating this condition before surgery.
7Treatment groups
Experimental Treatment
Group I: Window Phase Arm C: Anastrozole + DegarelixExperimental Treatment2 Interventions
Participants will be randomly assigned to receive Anastrozole 1x daily for 3 weeks (21days) and Degarelix on day 1 only.
Group II: Window Phase Arm B: AnastrozoleExperimental Treatment1 Intervention
Participants will be randomly assigned to receive Anastrozole 1x daily for 3 weeks (21days).
Group III: Window Phase Arm A: TamoxifenExperimental Treatment1 Intervention
Participants will be randomly assigned to receive Tamoxifen 1x daily for 3 weeks (21days).
Group IV: Neoadjuvant Phase Arm G: Anastrozole + Degarelix + AbemaciclibExperimental Treatment3 Interventions
Participants will be randomly assigned to receive Anastrozole 1x daily, Degarelix on day 1 of each cycle and Abemaciclib 2x daily for 4 cycles (4 months); each study cycle is 28 days.
Group V: Neoadjuvant Phase Arm F: Anastrozole and DegarelixExperimental Treatment2 Interventions
Participants will be randomly assigned to receive Anastrozole 1x daily and Degarelix on day 1 of each cycle for 4 cycles (4 months); each study cycle is 28 days.
Group VI: Neoadjuvant Phase Arm E: Tamoxifen + AbemaciclibExperimental Treatment2 Interventions
Participants will be randomly assigned to receive Tamoxifen 1x daily and Abemaciclib 2x daily for 4 cycles (4 months); each study cycle is 28 days.
Group VII: Neoadjuvant Phase Arm D: TamoxifenExperimental Treatment1 Intervention
Participants will be randomly assigned to receive Tamoxifen 1x daily for 4 cycles (4 months); each study cycle is 28 days.
Abemaciclib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Verzenio for:
- Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
- HR+, HER2- node-positive early breast cancer
🇪🇺 Approved in European Union as Verzenio for:
- HR+, HER2- advanced or metastatic breast cancer
- HR+, HER2- node-positive early breast cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Georgetown University Medical CenterWashington, United States
Mayo ClinicRochester, MN
Dana Farber Cancer InstituteBoston, MA
UNC Lineberger Comprehensive Cancer CenterChapel Hill, NC
More Trial Locations
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Who Is Running the Clinical Trial?
Jose Pablo LeoneLead Sponsor
Eli Lilly and CompanyIndustry Sponsor
Translational Breast Cancer Research Consortium (TBCRC)Collaborator
References
Pharmacotherapy for male breast cancer. [2019]Breast cancer in males is uncommon, occurring at approxiamtely 1% of the rate of female breast cancer. Male breast carcinomas tend to be highly positive for hormone receptors, including oestrogen, progesterone and androgen receptors. Owing to this, hormone therapy is recommended as the primary treatment modality. Adjuvant therapy is recommended for male breast cancers with large size or positive axillary nodes. For metastatic disease, options for therapy include tamoxifen, orchiectomy, anti-androgens with or without luteinising hormone releasing hormone analogues or combination chemotherapy. The newer hormonal treatments, such as the selective aromatase inhibitors or novel antioestrogens, have not yet been well studied in male breast cancer but have potential for efficacy in this disease.
Clinical, Pathological, and Prognostic Features of Male Breast Cancer: A Multicenter Study. [2023]Male breast cancer (BC) represents less than 1% of male tumors. Little is known about male BC characteristics, management, and survival, with many studies based on a small number of cases. Consequently, the treatment of male BC lacks specific guidelines. The aims of the study are to compare male and female breast cancer (FBC) in terms of cancer clinical and anatomopathological features and treatment approach, and to identify differences between male BC and FBC in terms of survival. Patients and methods: Data from 2006 to 2018 were retrospectively acquired. Amounts of 49 males and 680 postmenopausal females with primary non-metastatic BC who underwent breast surgery at Mauriziano Hospital or IRCCS Candiolo (TO-Italy) were included. The mean age at diagnosis for male BC was 68.6 years, and males presented a smaller tumor size than women (p < 0.05) at diagnosis. Most male BC patients received adjuvant endocrine therapy (AET) with tamoxifen (73.5%). AET drop-out rate due to side effects was 16.3% for males compared to 7.6% for women (p = 0.04). Comparing FBC and male BC, no differences have been identified in terms of DFS and OS, with a similar 10-year-relapse rate (12% male BC vs. 12.4% FBC). Propensity Score Matching by age, nodal status, pT, and molecular subtype had been performed and no differences in OS and DFS were seen between male BC and FBC. In conclusion, male BC and FBC have similar prognostic factors and survival outcomes. The drop-out rate of AET was higher in males, and side effects were the main reason for drug discontinuation.
Hormonal therapy for male breast cancer: A different approach for a different disease. [2022]Male breast cancer (MBC) is on the rise in the United States [Surveillance, Epidemiology, and End Results (SEER) Program () SEER Stat Database: Incidence-SEER 9 Regs Public-Use; November 2004 submission (1973-2002), National Cancer Institute, DCPPS, Surveillance Research Program, Cancer Statistics Branch, released April 2005, based on the November 2004 submission]; however mortality due to MBC has not changed unlike in its female counterpart [American Cancer Society: Cancer facts and figures 2005. Atlanta (GA): American Cancer Society; 2005]. The rarity of MBC has precluded major progress in the understanding and treatment of this disease. Treatment has often been extrapolated from female breast cancer (FBC) despite distinct clinicopathologic features between the two entities, especially with regards to the role of male hormones and estrogens in this disease. Also, it is uncertain if hormone receptor positive tumors carry the same prognostic implication in MBC as in the female disease. Hormonal therapy has been the mainstay of treatment in MBC with tamoxifen the front-line drug. The role of the newer generation aromatase inhibitors has not been well defined but they are being used in clinical practice for the treatment of MBC, based on accepted data for women with the disease. This commentary focuses on the major hormonal differences between male and female breast cancer that would suggest the need to explore different treatment strategies if significant advances are to be made in the understanding and treatment of this distinct disease.
[Systemic therapy of male breast cancer]. [2018]Due to its low incidence there is only few information on optimal systemic therapy of male breast cancer. There are no prospective randomized trials, neither for early breast cancer nor for advanced stages. Retrospective analyses mostly comprise long-term-data from a small number of patients. In terms of epidemiology, cellular receptors or genetics there exist some significant differences between male and female breast cancer. Therefore, the possibility to extrapolate treatment recommendation for male patients from female breast cancer-trials is limited. Despite a high rate of receptor positivity, hormonal therapy seems to be less efficient in men, possibly due to different biological factors. The current standard in endocrine therapy is tamoxifen. It is not known whether tamoxifen therapy is as effective as orchiectomy, but tamoxifen is favoured because of its low side effects. The use of aromatase inhibitors needs to be considered carefully, since aromatization is blocked, but 5-alpha-reductase increases estrogen-like androstanediole. There might be a benefit from additional therapy with GnRH-analoga respectively 5-alpha-reductase inhibitors, but data is not available yet. Combination of GnRH-analoga and antiandrogens does induce tumor remission, but comparison to other endocrine therapies is still lacking. Currently, the efficiency of fulvestrant, an estrogen receptor destructor, is being examined. Cytostatic therapy seems to be as effective as in female breast cancer patients. Nevertheless, convincing prospective trials for the management of early and advanced male breast cancer need to be performed.
A role for the androgen receptor in the treatment of male breast cancer. [2016]Male breast cancer (BC) is relatively rare, making up less than 1% of all breast cancer cases in the United States. Treatment guidelines for male BC are derived from studies on the treatment of female BC, and are based molecular and clinical characteristics, such as hormone receptor positivity. For female estrogen receptor positive (ER+) breast cancers, the standard of care includes three classes of endocrine therapies: selective estrogen receptor modulators, aromatase inhibitors, and pure anti-estrogens. In contrast to female ER+ breast cancers, there is less known about the optimal treatment for male ER+ BC. Furthermore, in contrast to ER, less is known about the role of the androgen receptor (AR) in male and female BC. We report here the treatment of a 28-year-old man with metastatic AR+, ER+ breast cancer otherwise refractory to chemotherapy, who has had a durable clinical response to hormonal suppression with the combination of aromatase inhibition (Letrozole) in conjunction with a GnRH agonist (Leuprolide).
Exploratory study of drug plasma levels during bicalutamide 150 mg therapy co-administered with tamoxifen or anastrozole for prophylaxis of gynecomastia and breast pain in men with prostate cancer. [2018]A randomized multicenter (14 centers) trial was conducted in 114 men with prostate cancer to determine whether the antiestrogen tamoxifen ('Nolvadex') 20 mg or the aromatase inhibitor anastrozole ('Arimidex') 1 mg prevent gynecomastia and breast pain during treatment with the non-steroidal antiandrogen bicalutamide ('Casodex') 150 mg, without compromising efficacy, safety, or quality of life. Plasma samples were collected in a subgroup of these patients to investigate whether trough (pre-dose) concentrations of bicalutamide 150 mg are influenced by concomitant administration of tamoxifen 20 mg or anastrozole 1 mg; the results of this pilot study are reported in this article.
Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients. [2022]Although an uncommon disease, male breast cancer (MBC) will be responsible for 300 deaths in 1993 in the United States. Because of the high rate of estrogen receptor positivity in males, adjuvant hormonal therapy with tamoxifen in the adjuvant setting has been used widely. Little is known about the side effects of this estrogen receptor blocker in males.
Treatment of bicalutamide-induced breast events. [2014]Bicalutamide is a competitive nonsteroidal androgen receptor antagonist. In the European Union and a number of other countries, bicalutamide 150 mg per day is approved as an adjuvant to primary treatments (radical prostatectomy or radiotherapy) or as monotherapy as an alternative to surgical or medical castration in men with locally advanced, nonmetastatic prostate cancer. The ongoing bicalutamide Early Prostate Cancer (EPC) program has shown that breast events, defined as gynecomastia, breast pain or both, are a significant limitation of bicalutamide. Nearly 90% of patients experienced one or both symptoms and nearly 16% of patients withdrew from the EPC program as a consequence of bicalutamide-induced breast events. Tamoxifen, anastrozole and radiotherapy have all been studied as options for the treatment of breast events. To date, tamoxifen appears to be the superior agent in terms of outcomes; however, further studies are still required to determine the optimal dose and timing of tamoxifen administration for both prophylaxis and treatment. In addition, the impact on prostate cancer control remains uncertain. An ongoing clinical trial using toremifene to prevent morphometric vertebral fractures in men undergoing medical and/or surgical castration will provide some additional data on the effects of selective estrogen receptor modulators in men with prostate cancer.
Potential benefit of maintenance trastuzumab and anastrozole therapy in male advanced breast cancer. [2018]Less than 1% of breast cancers occur in males, and the optimal hormonal therapy in this setting is unknown. Tamoxifen is effective in this entity, but unfortunately there is little information on aromatase inhibitors (AI) or fulvestrant. It has been suggested that the association of AI and GnRh analogues and AI could block the two routes of oestrogen production in males, and therefore this approach could increase efficacy. However, it could also enhance the rate of adverse events (hot flashes, sexual impotence, etc.). In this report we report 11 months of progression-free survival, without any adverse events, in a patient who received trastuzumab and anastrozole therapy. We conclude that this combination is a reasonable option in men with ER+ and Her2+ advanced breast cancer.
Aromatase inhibitors and male breast cancer. [2019]The majority of breast cancers in male patients are hormone receptor positive. Tamoxifen has proven to be successful in both adjuvant and metastatic settings and remains the standard of care. Given the improved outcomes in female patients with aromatase inhibitors (AI), these drugs have become a potential therapeutic tool for male patients. Preliminary data show effective suppression of oestradiol levels in males treated with AI and some reports have demonstrated objective responses. Here we report a case of a male patient with metastatic breast cancer treated with letrozole who achieved clinical response associated with a decrease in blood oestradiol levels.
How to treat male breast cancer. [2019]The prevalence for breast cancer in males in Europe is estimated to be 1 or less per 100,000. Male breast cancer has a peak incidence at the age of 71 years. There are no randomized data giving information on the optimal therapy for male breast cancer patients, thereby limiting firmer conclusions. The preferred primary surgical therapy is modified radical/simple mastectomy, but breast-conserving surgery has also been used in males. Post-operative radiotherapy should be used on a more routine basis; as males have shorter breast-anatomical distances and males are diagnosed at a later stage compared with females. The so far preferred adjuvant therapy modality has been tamoxifen for patients with endocrine responsive disease. The use of aromatase inhibitors in males is more controversial, since they may not deplete the estradiol levels sufficiently. Different chemotherapy regimens have been used in the adjuvant and metastatic setting. The use of adjuvant therapy has in institutional and review comparisons been demonstrated to result in an improved outcome.
Male breast cancer. [2022]Treatments for men with breast cancer are based largely on accepted regimens for women with the disease. Surgical treatment of the primary tumor should be a mastectomy. Lymph node assessment can be done by conventional axillary node dissection or, similar to selected women with small primary tumors, by sentinel node dissection. Decisions regarding adjuvant systemic treatment should be made on the same basis as for women. Axillary node status, tumor size, hormone receptor status, and the health of the patient are important considerations in determining what adjuvant treatment is offered. The role of radiation after mastectomy in men is not well defined, but radiation should be used in patients at high risk for local recurrence. For patients with metastatic disease, treatment is based on the hormone receptor status of the tumor and is similar to the treatment for women. Because most men with breast cancer have hormone receptor-positive disease, hormonal therapy is a mainstay of treatment and tamoxifen remains the front-line drug of choice, although the latest generation of aromatase inhibitors have supplanted tamoxifen as a first-line therapy for women. As a second-line hormonal therapy for men, orchiectomy or a luteinizing hormone-releasing hormone agonist with or without an antiandrogen are reasonable alternatives. There are no reports regarding the use of the antiestrogen fulvestrant in men, but its mechanism of action and efficacy in women suggest that it will be a useful agent in hormone receptor-positive male breast cancer. For men with hormone-resistant disease, palliative chemotherapy with the same agents used for treatment of women with breast cancer is appropriate.