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

A Study Evaluating the Pregnancy Outcomes and Safety of Interrupting Endocrine Therapy for Young Women With Endocrine Responsive Breast Cancer Who Desire Pregnancy

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Early Breast Cancer
• Intervention / Treatment: Other: Endocrine therapy interruption

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
• Enrollment (Actual): 518
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6008
      • St John of God Subiaco Hospital
• Austria
  • Graz, Austria, 8036
    • Univ. Klinik f. Frauenheilkunde u. Geburtshilfe
  • Innsbruck, Austria, 6020
    • Univ. Klinik f. Frauenheilkunde Innsbruck
  • Salzburg, Austria, 5020
    • LKH Salzburg
  • Vienna, Austria, 1090
    • Med. Univ. Klinik f. Chir
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-luc
  • Brussels, Belgium
    • Institut Jules Bordet
  • Brussels, Belgium
    • Cliniques Universitaires Saint-Luc Brussels
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Liège, Belgium, 4000
    • C.H.U. Sart-Tilman
  • Namur, Belgium, 5000
    • Clinique St.Elizabeth
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver Cancer Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • St Michael's Hospital
    • Toronto, Ontario, Canada
      • Odette Cancer Centre - Sunnybrook Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • CHUM - Centre Hospitalier de l'Universite de Montreal
    • Québec, Quebec, Canada, G1S 4L8
      • CHA-Hopital Du St-Sacrement
    • Sherbrooke, Quebec, Canada
      • Centre Hospitalier Universitaire de Sherbrooke
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69373
    • French Lyon Cancer Center
  • Paris, France
    • APHP, Tenon Hospital in Paris
• Greece
  • Athens, Greece
    • Laso General Hospital, First Department of Medical Oncology
  • Crete
    • Stavrakia, Crete, Greece, 71110
      • University General Hospital of Heraklion
• Hungary
  • Debrecen, Hungary
    • Debrecen University Dep. of Oncology
• Ireland
  • Dublin, Ireland
    • St Vincent's University Hospital
  • Dublin, Ireland
    • St. James's Hospital
  • Galway, Ireland
    • Galway University Hospital
  • Limerick, Ireland
    • University Hospital Limerick
  • Waterford, Ireland
    • University Hospital Waterford
• Israel
  • Jerusalem, Israel
    • Shaare Zedek Medical Center
  • Tel Litwinsky, Israel, 5265601
    • Chaim Sheba Medical Center
• Italy
  • Aviano, Italy, 33081
    • Centro Di Riferimento Oncologico
  • Biella, Italy
    • Ospedale degli Infermi - S. C. Oncologia Medica
  • Bolzano, Italy, 39100
    • Azienda Sanitaria di Bolzano
  • Genova, Italy
    • Istituto Nazionale Ricerca Cancro
  • Meldola, Italy
    • Istituto scientifico Romagnolo per lo studio e la cura
  • Milan, Italy, 20141
    • Istituto Europeo di Oncologia (IEO)
  • Novara, Italy, 28100
    • University of Eastern Piedmont
  • Pavia, Italy, 27100
    • Salvatore Maugeri Foundation - Medical Oncology Unit
  • Rimini, Italy, 47923
    • UO Oncologia, Rimini Hospital
  • Rome, Italy
    • Regina Elena National Cancer Institute
  • Varese, Italy, 21100
    • AO Universitaria Ospedale Di Circolo e Fondazione
  • Viterbo, Italy
    • Ospedale Belcolle di Viterbo
  • Firenze
    • Prato, Firenze, Italy
      • Ospedale di Prato
  • Modena
    • Carpi, Modena, Italy, 41012
      • U.O Medicina Oncologica Ospedale di Carpi
  • Trento
    • Trento, Trento, Italy, 38122
      • Ospedale di Trento
  • Vareze
    • Castellanza, Vareze, Italy
      • Multimedica Spa
• Japan
  • Fukuoka, Japan, 811-1395
    • NHO Kyushu Cancer Centre, 3-1-1 Notame Minami-ku Fukuoka-shi
  • Kagoshima, Japan
    • Social Medical Corporation Hakuaikai Sagara Hospital
  • Kawasaki, Japan
    • St Marianna University School of Medicine Hospital
  • Kyoto, Japan
    • Kyoto University Hospital
  • Matsuyama, Japan
    • Nho Shikoku Cancer Center
  • Minato-ku, Tokyo, Japan, 105-8470
    • Toranomon Hospital
  • Nagoya, Japan, 463-0802
    • Kamiiida daiichi General Hospital
  • Okayama, Japan
    • Okayama University Hospital
  • Sendai, Japan
    • Tohoku University Hospital
  • Tokyo, Japan
    • National Cancer Center Hospital
  • Tokyo, Japan
    • Showa University Hospital
  • Tokyo, Japan
    • The Cancer Institute Hospital Of JFCR
  • Tokyo, Japan
    • National Cancer Center for Global Medicine
  • Tokyo, Japan
    • St Luke's International Hospital
  • Tsukuba, Japan
    • University of Tsukuba
  • Ōsaka, Japan
    • NHO Osaka National Hospital
  • Hyōgo
    • Amagasaki, Hyōgo, Japan, 660-8511
      • Kansai Rosai Hospital
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan
      • Seirei Hamamatsu General Hospital
• Lebanon
  • Beirut, Lebanon
    • American University of Beirut Medical Center
• Netherlands
  • Leiden, Netherlands, 2300 RC
    • Leiden University Medical Centre, Albinusdreef 2, Postbus 9600
• Norway
  • Oslo, Norway
    • Norwegian Radium Hospital (Oslo University)
• Portugal
  • Lisbon, Portugal
    • Champalimaud Cancer Center - Breast Cancer Unit
• Serbia
  • Belgrade, Serbia
    • Institute of Oncology & Radiology of Serbia
• Slovenia
  • Ljubljana, Slovenia
    • Institute of Oncology Ljubljana - Medical Oncology Department
• South Korea
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea
    • Asan Medical Center
  • Seoul, South Korea
    • Seoul National University Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain
    • Hospital General De Catalunya
  • Donostia / San Sebastian, Spain
    • Hospital Universitario Donostia
  • Girona, Spain
    • Instituto Catalán de Oncología de Gerona Hospital
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Madrid, Spain
    • Hospital Universitario de Fuenlabrada
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro - Centro Integral Oncologico Clara Campal (CIOCC)
  • Málaga, Spain, 29010
    • Hospital Clinico Universitario Virgen de la Victoria
  • Oviedo, Spain
    • Hospital Universitario Central de Asturias
  • Palma, Spain
    • Hospital Son Espases, Palma de Mallorca
  • Pamplona, Spain
    • Complejo Hospitalario de Navarra
  • Santiago de Compostela, Spain
    • Complejo Hospitalario Universitario de Santiago
  • Seville, Spain
    • Hospital Quiron Sagrado Corazon
  • Seville, Spain, 41013
    • Universitario Virgen del Rocio
  • Toledo, Spain
    • Hospital Virgen de la Salud
  • Valencia, Spain
    • Hospital General Universitario de Valencia - Servico Oncologia
  • Zaragoza, Spain
    • Hospital Clinico Universitario Lozano Blesa
  • Murcia
    • El Palmar, Murcia, Spain
      • Hospital Clínico Universitario Virgen de la Arrixaca
• Switzerland
  • Baden, Switzerland, 5404
    • Kantonspital Baden AG
  • Basel, Switzerland, 4031
    • Universitätsspital Basel
  • Bellinzona, Switzerland
    • Istituto Oncologico Della Svizzera Italiana (IOSI)
  • Bern, Switzerland, 3012
    • Oncocare Bern
  • Frauenfeld, Switzerland
    • Brustzentrum Thurgau - Obstetrics and Gynecology
  • Geneva, Switzerland, 1211
    • University Hospital Geneva
  • Lausanne, Switzerland
    • University Hospital of Lausanne (CHUV) BH06 - Oncology Department
  • Sankt Gallen, Switzerland, 9007
    • Brustzentum Kantonsspital St. Gallen
  • Sion, Switzerland, 736
    • CHCVs Hôpital de Sion - Service d'oncologie ambulatoire
  • Zurich, Switzerland, 8091
    • University Hospital Zurich
  • Zurich, Switzerland, 8008
    • Brust-Zentrum AG
  • Canton of Bern
    • Bern, Canton of Bern, Switzerland, 3010
      • Inselspital Bern
    • Thun, Canton of Bern, Switzerland, 3600
      • Spital STS AG Onkologiezentrum Thun-Berner Oberland
• United States
  • California
    • Los Angeles, California, United States, 90211
      • Cedars Sinai Medical Centre
    • Palo Alto, California, United States, 94305
      • Stanford Cancer Institute
    • San Diego, California, United States
      • Sharp Memorial Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Centre - Anschutz Cancer Pavilion
    • Boulder, Colorado, United States, 80303
      • Rocky Mountain Cancer Center
    • Denver, Colorado, United States, 80218
      • SCL Health Saint Joseph Hospital
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
  • Connecticut
    • Derby, Connecticut, United States, 06418
      • Smilow Cancer Hospital-Derby Care Center
    • Fairfield, Connecticut, United States, 06824
      • Smilow Cancer Hospital Care Center-Fairfield
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
    • New Haven, Connecticut, United States, 06520
      • Yale University - Yale Cancer Centre
    • North Haven, Connecticut, United States, 06473
      • Yale-New Haven Hospital North Haven Medical Center
    • Orange, Connecticut, United States, 06477
      • Smilow Cancer Hospital-Orange Care Center
    • Torrington, Connecticut, United States, 06790
      • Smilow Cancer Hospital-Torrington Care Center
    • Trumbull, Connecticut, United States, 06611
      • Smilow Cancer Hospital Care Center-Trumbull
    • Waterbury, Connecticut, United States, 06708
      • Smilow Cancer Hospital-Waterbury Care Center
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
    • Newark, Delaware, United States, 19713
      • Helen F. Graham Cancer Center
    • Newport, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants PA
    • Newport, Delaware, United States, 19713
      • Regional Hematology Oncology Practice Associates
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20016
      • Sibley Memorial Hospital
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • OnCare Hawaii-Kuakini
    • Honolulu, Hawaii, United States, 96701
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96813
      • OnCare Hawaii Inc - POB I
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Centre
  • Illinois
    • Chicago, Illinois, United States, 60612
      • John H Stroger Jr Hospital of Cook County
    • Danville, Illinois, United States, 61832
      • Carle on Vermilion
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group - Effingham
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Evanston, Illinois, United States, 60201
      • Northwestern University
    • Glenview, Illinois, United States, 60026
      • NorthShore University Health System - Glenbrook Hospital
    • Highland Park, Illinois, United States, 60035
      • NorthShore Unversity Health System - Highland Park Hospital
    • Mattoon, Illinois, United States, 61938
      • Mattoon Charleston Primary Care
    • Skokie, Illinois, United States, 60076
      • NorthShore Medical Centre
    • Urbana, Illinois, United States, 61801
      • The Carle Foundation Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Centre
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Johns Hopkins University
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Centre
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-5450
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48103
      • Saint Joseph Mercy Hospital
    • Brighton, Michigan, United States, 48114
      • IHA Hematology Consultants-Brighton
    • Brighton, Michigan, United States, 48114
      • Saint Joseph Mercy Hospital - Brighton
    • Canton, Michigan, United States, 48188
      • IHA Hematology Consultants-Canton
    • Canton, Michigan, United States, 48188
      • Saint Joseph Mercy Hospital- Canton
    • Chelsea, Michigan, United States, 48118
      • IHA Hematology Consultants-Chelsea
    • Chelsea, Michigan, United States, 48118
      • Saint Joseph Mercy Hospital - Chelsea
    • Ypsilanti, Michigan, United States, 48198
      • IHA Hematology Oncology Consultants-Ann Arbor
  • Minnesota
    • Bemidji, Minnesota, United States, 56501
      • Sanford Clinic North - Bemidji
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Duluth, Minnesota, United States, 55805-1951
      • Essentia Health Cancer Center
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Maplewood, Minnesota, United States, 55109
      • St John's Hospital
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital, 800 East 28th Street
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center - Cancer Center
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
    • Saint Louis Park, Minnesota, United States, 55343
      • Park Nicollet Methodist Hospital
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
  • Missouri
    • St Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
  • Montana
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center/Norris Cotton Cancer Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Weill Medical College of Cornell University
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center-Weiler Hospital
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center - Einstein Campus, 1695 Eastchester Road
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center - Moses Campus, 111 East 210th Street
    • White Plains, New York, United States, 10601
      • Dickstein Cancer Treatment Centre
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Clinton, North Carolina, United States, 28328
      • Southeastern Medical Oncology Centre
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Centre
    • Hendersonville, North Carolina, United States
      • Margaret R Pardee Memorial Hospital
    • Jacksonville, North Carolina, United States, 28546
      • Southeastern Medical Oncology Centre
    • Wilson, North Carolina, United States, 27534
      • Southeastern Medical Oncology Centre
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismark Medical Centre
    • Fargo, North Dakota, United States, 58102
      • Sanford Roger Maris Cancer Centre
    • Fargo, North Dakota, United States, 58122
      • Sanford Medical Centre
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Columbus, Ohio, United States, 43210
      • Ohio State University
    • Orange, Ohio, United States, 44122
      • Chagrin Highlands
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC-Magee Womens Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital of Rhode Island
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Faris
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Butternut
    • Greenville, South Carolina, United States, 29611
      • Greenville Health System Cancer Institute-Eastside
    • Greer, South Carolina, United States, 29650
      • Greenville Health System Cancer Institute-Greer
    • Seneca, South Carolina, United States, 29672
      • Greenville Health System Cancer Institute-Seneca
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
    • Spartanburg, South Carolina, United States, 29307
      • Greenville Health System Cancer Institute-Spartanburg
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Centre Oncology Clinic
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford USD Medical Centre - Sioux Falls
  • Texas
    • Laredo, Texas, United States, 78045
      • Doctor's Hospital of Laredo
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute / University of Utah
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Centre
  • Virginia
    • Mechanicsville, Virginia, United States, 23116
      • Bon Secours Memorial Regional Medical Centre
    • Midlothian, Virginia, United States, 23114
      • Bon Secours Saint Francis Medical Centre
    • Richmond, Virginia, United States, 23223
      • Bon Secours Saint Mary's Hospital
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 42 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endocrine therapy interruption; Endocrine therapy interruption after having completed between ≥ 18 months and ≤ 30 months.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breast Cancer free interval (BCFI)	Kaplan-Meier Analysis	From enrollment until the first invasive BC event, assessed up to 14 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: ETOP IBCSG Partners Foundation
• 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)

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• Demeestere I, Niman SM, Partridge AH, Diego DS, Kammler R, Ruggeri M, Colleoni M, Shimizu C, Saura C, Gelmon KA, Saetersdal AB, Kroep JR, Mailliez A, Amant F, Ruiz-Borrego M, Lee JE, Kataoka A, Walshe JM, Takei J, Borstnar S, Borges VF, Saunders C, Susnjar S, Bjelic-Radisic V, Cardoso F, Meisel JL, Kawwass JF, Spanic T, El-Abed S, Piccart M, Korde LA, Goldhirsch A, Gelber RD, Pagani O, Azim HA Jr, Peccatori FA; International Breast Cancer Study Group and the POSITIVE Trial Collaborators. Hormonal factors predictive of fertility in patients with breast cancer interrupting adjuvant endocrine therapy to attempt pregnancy in POSITIVE trial. Breast. 2025 Oct;83:104547. doi: 10.1016/j.breast.2025.104547. Epub 2025 Jul 26.
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Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2014
• Primary Completion (Actual): May 15, 2025
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 21, 2014
• First Submitted That Met QC Criteria: December 2, 2014
• First Posted (Estimated): December 4, 2014

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Pregnancy; Breast; Premenopausal; endocrine responsive
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• 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)