Endocrine Therapy Interruption for Breast Cancer During Pregnancy

(POSITIVE Trial)

Recruiting at 210 trial locations

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: International Breast Cancer Study Group

Must be taking: Endocrine therapy

Disqualifiers: Post-menopausal, Metastatic cancer, Noncompliance, others

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

Compensation: Varies

Number of Visits: 1

518 Participants Needed

Trial Summary

What is the purpose of this trial?

The best available evidence suggests that pregnancy after breast cancer does not increase a woman's risk of developing a recurrence from her breast cancer. In particular, the most recent data suggest that this is the case also in women with a hormone receptor-positive breast cancer. There is also no indication of increased risk for delivery complications or for the newborn. The aim of the study is to investigate if temporary interruption of endocrine therapy, with the goal to permit pregnancy, is associated with a higher risk of breast cancer recurrence.The study aims also to evaluate different specific indicators related to fertility, pregnancy and breast cancer biology in young women. A psycho-oncological companion study on fertility concerns, psychological well-being and decisional conflicts will be conducted in interested Centers.

Will I have to stop taking my current medications?

The trial requires participants to stop their current endocrine therapy within 1 month prior to enrollment. This is to allow for a temporary interruption of the therapy to permit pregnancy.

What data supports the effectiveness of the treatment Endocrine therapy interruption for breast cancer during pregnancy?

Research from the POSITIVE trial indicates that young women with hormone-responsive breast cancer can safely pause endocrine therapy to try for pregnancy without increasing their short-term risk of cancer returning. ^{1 2 3 4 5}

Is endocrine therapy generally safe for humans?

Endocrine therapy, used for breast cancer, can have side effects that affect quality of life, but it is a common treatment and has been shown to reduce cancer recurrence. The safety and side effects can vary based on the specific drugs used, such as tamoxifen and aromatase inhibitors, and the patient's individual health factors. ^{6 7 8 9 10}

How does the treatment of endocrine therapy interruption for breast cancer during pregnancy differ from other treatments?

This treatment is unique because it allows women with hormone-responsive breast cancer to temporarily stop their endocrine therapy to attempt pregnancy without increasing the short-term risk of cancer relapse, which is not typically recommended with standard endocrine therapies. ^{2 3 4 11 12}

Research Team

Olivia Pagani, MD

Principal Investigator

Oncology Institue of Southern Switzerland (IOSI)

Eligibility Criteria

This trial is for premenopausal women aged 18-42 who had breast cancer and wish to become pregnant. They must have completed at least 18 months of endocrine therapy, be without current cancer evidence, and agree to follow-up and data handling. Women with BRCA mutations or prior treatments within a clinical trial are eligible.

Inclusion Criteria

I have been part of a clinical trial for hormone therapy or received preventive drug treatment.

I want to become pregnant.

Patient must be accessible for follow-up

Exclusion Criteria

I do not have any health conditions that would make it unsafe for me to join the study.

I have or had another type of cancer besides breast cancer.

I have had a hysterectomy, both ovaries removed, or radiation to the ovaries.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Endocrine Therapy Interruption

Participants interrupt endocrine therapy after having completed between ≥ 18 months and ≤ 30 months to permit pregnancy

3 months

1 visit (in-person) for therapy interruption

Pregnancy Attempt

Participants attempt conception after a safe period post-endocrine therapy interruption

Up to 24 months

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pregnancy outcomes and breast cancer recurrence

Up to 14 years

Annual visits (in-person)

Treatment Details

Interventions

• Endocrine therapy interruption

Trial Overview The study tests the safety of temporarily stopping endocrine therapy in young women who want to get pregnant after breast cancer treatment. It will assess the risk of cancer recurrence and examine fertility, pregnancy outcomes, and psychological well-being related to fertility concerns.

Participant Groups

Group I: Endocrine therapy interruption Experimental Treatment 1 Intervention

Endocrine therapy interruption after having completed between ≥ 18 months and ≤ 30 months.

Who Is Running the Clinical Trial?

International Breast Cancer Study Group

Lead Sponsor

Trials

29

Recruited

25,100+

ETOP IBCSG Partners Foundation

Lead Sponsor

Trials

66

Recruited

58,200+

Alliance for Clinical Trials in Oncology

Collaborator

Trials

521

Recruited

224,000+

Canadian Cancer Trials Group

Collaborator

Trials

135

Recruited

70,300+

Breast International Group

Collaborator

Trials

34

Recruited

53,600+

Findings from Research

A 50-year-old breast cancer patient experienced significant adverse effects from tamoxifen, including hot flushes, hyperhidrosis, urinary frequency, and depression, which negatively impacted her quality of life.

After 25 days of treatment with traditional Korean herbal medicine and acupuncture, the patient's symptoms improved significantly, indicating that these interventions may help alleviate tamoxifen-induced side effects in breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Traditional Korean medicine treatment for tamoxifen associated adverse events of breast cancer patient: A CARE - Compliant case report. Seo, J., Lee, D., Jo, HG.[2021]

Endocrine therapy is essential for treating premenopausal women with early-stage hormone receptor-positive breast cancer, but there is still uncertainty about the best strategies for using tamoxifen and estrogen deprivation alongside chemotherapy.

Research is ongoing to find better markers for predicting how well patients will respond to endocrine therapy and to understand the unique side effects that young women may experience from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant hormonal therapy for premenopausal women with breast cancer. Brown, RJ., Davidson, NE.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Extended endocrine therapy in early breast cancer: how long and who for? [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Women with Breast Cancer Can Attempt Pregnancy. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

The Effect of Subsequent Pregnancy on Prognosis in Young Breast Cancer Patients (≤35 Years Old) According to Hormone Receptor Status. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Who are the women who enrolled in the POSITIVE trial: A global study to support young hormone receptor positive breast cancer survivors desiring pregnancy. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Endocrine treatment and incidence of relapse in women with oestrogen receptor-positive breast cancer in Europe: a population-based study. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Traditional Korean medicine treatment for tamoxifen associated adverse events of breast cancer patient: A CARE - Compliant case report. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

[Hormone therapy in invasive breast cancer : update 2016]. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Adjuvant hormonal therapy for premenopausal women with breast cancer. [2015]

9. Germany pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors for breast cancer. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Current controversies in the endocrine therapy of advanced breast cancer. [2018]

11. Australia pubmed.ncbi.nlm.nih.gov

Clinical consultations and investigations before and after discontinuation of endocrine therapy in women with primary breast cancer. [2018]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Update on the Management of Breast Cancer during Pregnancy. [2020]