Pregnancy Outcome and Safety of Interrupting Therapy for Women With Endocrine Responsive Breast Cancer (POSITIVE)

• ClinicalTrials.gov Identifier: NCT02308085
• Recruitment Status: Active, not recruiting
• First Posted: December 4, 2014
• Last Update Posted: March 16, 2023
• Sponsor: ETOP IBCSG Partners Foundation
• Collaborators: Alliance for Clinical Trials in Oncology; Canadian Cancer Trials Group; Breast International Group
• Information provided by (Responsible Party): ETOP IBCSG Partners Foundation

Tracking Information

• First Submitted Date: November 21, 2014
• First Posted Date: December 4, 2014
• Last Update Posted Date: March 16, 2023
• Actual Study Start Date: December 4, 2014
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 2, 2014)

Breast Cancer free interval (BCFI) [ Time Frame: From enrollment until the first invasive BC event, assessed up to 14 years ]

Kaplan-Meier Analysis

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 2, 2014)

• Information on Menstruation recovery and pattern [ Time Frame: Up to 24 months after enrollment ]
  Menstrual diary
• Pregnancy rate (determined by pregnancy test) [ Time Frame: Up to 24 months after enrollment ]
  Pregnancy test
• Pregnancy outcome [ Time Frame: Up to 33 months after enrollment ]
  Labor and delivery Information, full term pregnancy, caesarean section, abortion, miscarriage, ectopic, stillbirth rates.
• Offspring outcome [ Time Frame: Up to 33 months after enrollment ]
  Collect information on preterm birth, low birth weight, births defects rates.
• Breastfeeding pattern [ Time Frame: Up to 36 months after enrollment ]
  Analysis of pattern e.g Duration, use of ipsilateral breast if previous breast conservation, side exclusivity
• Use of assisted reproductive Technology (ART) [ Time Frame: Up to 24 months after enrollment ]
  ART use will be tabulated
• Distant recurrence-free interval (DRFI) [ Time Frame: Time from enrollment in the study to the first breast cancer recurrence in a distant site, assessed up to 14 years ]
  Kaplan-Meier Analysis

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pregnancy Outcome and Safety of Interrupting Therapy for Women With Endocrine Responsive Breast Cancer
• Official Title: A Study Evaluating the Pregnancy Outcomes and Safety of Interrupting Endocrine Therapy for Young Women With Endocrine Responsive Breast Cancer Who Desire Pregnancy
• Brief Summary: 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.

Detailed Description

Recent decades have witnessed a delay in childbearing for a variety of reasons including cultural, educational, and professional. As a consequence, breast cancer in young women often occurs before the completion of reproductive plans. Infertility has a significant impact on quality of life, resulting in substantial distress in younger women with breast cancer and influencing treatment decisions in a consistent proportion of patients.The best available evidence suggests that pregnancy after breast cancer does not increase a woman's risk of developing a recurrence.For women desiring pregnancy after a breast cancer, 5-10 years of endocrine therapy may substantially reduce the chance of conception; however, a shorter duration of endocrine therapy in this population has not been studied in a prospective manner.

Birth outcome after breast cancer has not been shown to be different from that of the normal population, but increased risks of delivery complications, cesarean section, preterm birth and low birth weight have been reported.

Endocrine agents are potentially teratogenic: taking into account their median half-life, waiting 3 months after their interruption before attempting conception is considered safe.

The limited evidence available on breastfeeding after breast cancer reports successful lactation from the treated breast in approximately 30% of women without detrimental effect on survival. No prospective definitive data are available.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Early Breast Cancer

Intervention

Other: Endocrine therapy interruption

3 months wash-out between treatment interruption and pregnancy attempt. Up to 2 years interruption to allow pregnancy, delivery, breastfeeding or failure to conceive.

Endocrine therapy resumption. Completion of full duration of endocrine therapy according to individual risk, institutional policy or patient's preference.

Study Arms

Experimental: Endocrine therapy interruption

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

Intervention: Other: Endocrine therapy interruption

Publications *

• Brinton LA, Sherman ME, Carreon JD, Anderson WF. Recent trends in breast cancer among younger women in the United States. J Natl Cancer Inst. 2008 Nov 19;100(22):1643-8. doi: 10.1093/jnci/djn344. Epub 2008 Nov 11.
• Leclere B, Molinie F, Tretarre B, Stracci F, Daubisse-Marliac L, Colonna M; GRELL Working Group. Trends in incidence of breast cancer among women under 40 in seven European countries: a GRELL cooperative study. Cancer Epidemiol. 2013 Oct;37(5):544-9. doi: 10.1016/j.canep.2013.05.001. Epub 2013 Jun 12. Erratum In: Cancer Epidemiol. 2014 Feb;38(1):106. GRELL Working Group [added]; multiple investigator names added.
• Bentzon N, During M, Rasmussen BB, Mouridsen H, Kroman N. Prognostic effect of estrogen receptor status across age in primary breast cancer. Int J Cancer. 2008 Mar 1;122(5):1089-94. doi: 10.1002/ijc.22892.
• Anders CK, Hsu DS, Broadwater G, Acharya CR, Foekens JA, Zhang Y, Wang Y, Marcom PK, Marks JR, Febbo PG, Nevins JR, Potti A, Blackwell KL. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol. 2008 Jul 10;26(20):3324-30. doi: 10.1200/JCO.2007.14.2471. Erratum In: J Clin Oncol. 2011 Sep 20;29(27):3721.
• Perachino M, Poggio F, Arecco L, Blondeaux E, Spinaci S, Marrocco C, Levaggi A, Lambertini M. Update on Pregnancy Following Breast Cancer Diagnosis and Treatment. Cancer J. 2022 May-Jun 01;28(3):176-182. doi: 10.1097/PPO.0000000000000599.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 17, 2020): 518
• Original Estimated Enrollment (submitted: December 2, 2014): 500
• Estimated Study Completion Date: December 2028
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age ≥ 18 and ≤ 42 years at enrollment.
• Has received adjuvant endocrine therapy (SERM alone, GnRH analogue plus SERM or AI) for ≥18 months but ≤30 months for early breast cancer.

Note: Patients who have received neo/adjuvant endocrine treatment within a clinical trial and patients who have received pharmaco-prevention are eligible.

• The adjuvant endocrine therapy must have stopped within 1 month prior to enrollment.
• Patient wishes to become pregnant. Note: Patients who have undergone oocyte/embryo/ovarian tissue cryopreservation at breast cancer diagnosis and/or have a previous history of assisted reproductive technology (ART) are eligible.
• Breast cancer for which patient is receiving endocrine therapy must have been histologically-proven stage I-III, endocrine-responsive (i.e., estrogen and/or progesterone receptor positive, according to local definition of positive, determined using immunohistochemistry (IHC)), and treated with curative intent.

Note:

• Patients with synchronous bilateral invasive breast cancer (diagnosed histologically within 2 months) are eligible.
• Patient with invasive breast cancer or synchronous bilateral invasive breast cancer (diagnosed histologically within 2 months) during pregnancy are eligible.
• Patients with BRCA1/2 mutations are eligible.
• Patients could have received neo/adjuvant chemotherapy, or other systemic therapy (e.g., neo/adjuvant HER2-targeted therapy) according to institutional policy and patient's desire.
• Patient must be premenopausal at breast cancer diagnosis, as determined locally and documented in patient record.
• Patient must be without clinical evidence of loco-regional and distant disease, as evaluated according to institutional assessment standards and documented in the patient record.
• Written informed consent (IC) for trial participation must be signed and dated by the patient and the investigator prior to enrollment.
• Written consent to biological material submission, indicating the patient has been informed of and agrees to tissue and blood material use, transfer and handling, must be signed and dated by the patient and the investigator prior to any procedures specific for this trial.
• The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines.
• Patient must be accessible for follow-up.

Exclusion Criteria:

• Post-menopausal patients at BC diagnosis, as determined locally.
• History of hysterectomy, bilateral oophorectomy or ovarian irradiation.
• Patients with current local, loco-regional relapse and/or distant metastatic breast cancer.
• Patients with a history of prior (ipsi- and/or contralateral) invasive BC.
• Patients with previous or concomitant non-breast invasive malignancy.
• Exceptions are limited exclusively to patients with the following previous malignancies, if adequately treated: basal or squamous cell carcinoma of the skin, in situ non-breast carcinoma, contra- or ipsilateral in situ breast carcinoma, stage Ia carcinoma of the cervix.
• Concurrent disease or condition that would make the patient inappropriate for study participation or any serious medical disorder that would interfere with the patient's safety.
• Patients with a history of noncompliance to medical treatments and/or considered potentially unreliable.
• Patients with psychiatric, addictive, or any disorder that would prevent compliance with protocol requirements.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 42 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Canada, Denmark, France, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Lebanon, Netherlands, Norway, Portugal, Serbia, Slovenia, Spain, Switzerland, United States
• Removed Location Countries: Former Serbia and Montenegro

Administrative Information

• NCT Number: NCT02308085
• Other Study ID Numbers: IBCSG 48-14 / BIG 8-13; Alliance A221405 ( Other Identifier: Alliance for Clinical Trials in Oncology ); NCIC CTG MAC.18 ( Other Identifier: NCIC Clinical Trials Group )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: ETOP IBCSG Partners Foundation
• Original Responsible Party: Same as current
• Current Study Sponsor: ETOP IBCSG Partners Foundation
• Original Study Sponsor: Same as current

Collaborators

• Alliance for Clinical Trials in Oncology
• Canadian Cancer Trials Group
• Breast International Group

Investigators

• Study Chair: Olivia Pagani, MD; Oncology Institue of Southern Switzerland (IOSI)

• PRS Account: ETOP IBCSG Partners Foundation
• Verification Date: March 2023