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

Early Breast Cancer Clinical Trial

— POSITIVE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02308085
• Other study ID #: IBCSG 48-14 / BIG 8-13
• Secondary ID: Alliance A221405
• Status: Active, not recruiting
• Phase: N/A
• Start date: December 4, 2014
• Est. completion date: December 2028

Study information

• Verified date: April 2024
• Source: ETOP IBCSG Partners Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 518
• Est. completion date: December 2028
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 42 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• 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.

Locations

Country	Name	City	State
Australia	St John of God Subiaco Hospital	Perth	Western Australia
Austria	Univ. Klinik f. Frauenheilkunde u. Geburtshilfe	Graz
Austria	Univ. Klinik f. Frauenheilkunde Innsbruck	Innsbruck
Austria	LKH Salzburg	Salzburg
Austria	Med. Univ. Klinik f. Chir	Vienna
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Cliniques Universitaires Saint-Luc Brussels	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	UZ Leuven	Leuven
Belgium	C.H.U. Sart-Tilman	Liege
Belgium	Clinique St.Elizabeth	Namur
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	CHUM - Centre Hospitalier de l'Universite de Montreal	Montréal	Quebec
Canada	CHA-Hopital Du St-Sacrement	Quebec City	Quebec
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Odette Cancer Centre - Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	St Michael's Hospital	Toronto	Ontario
Canada	Vancouver Cancer Centre	Vancouver	British Columbia
Denmark	Rigshospitalet	København
France	Institut Bergonie	Bordeaux
France	Centre Oscar Lambret	Lille
France	French Lyon Cancer Center	Lyon
France	APHP, Tenon Hospital in Paris	Paris
Greece	Laso General Hospital, First Department of Medical Oncology	Athens
Greece	University General Hospital of Heraklion	Stavrakia	Crete
Hungary	Debrecen University Dep. of Oncology	Debrecen
Ireland	St Vincent's University Hospital	Dublin
Ireland	St. James's Hospital	Dublin 8
Ireland	Galway University Hospital	Galway
Ireland	University Hospital Limerick	Limerick
Ireland	University Hospital Waterford	Waterford
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Chaim Sheba Medical Center	Tel Hashomer
Italy	Centro di Riferimento Oncologico	Aviano
Italy	Ospedale degli Infermi - S. C. Oncologia Medica	Biella
Italy	Azienda Sanitaria di Bolzano	Bolzano
Italy	U.O Medicina Oncologica Ospedale di Carpi	Carpi	Modena
Italy	Multimedica Spa	Castellanza	Vareze
Italy	Istituto Nazionale Ricerca Cancro	Genova
Italy	Istituto scientifico Romagnolo per lo studio e la cura	Meldola
Italy	Istituto Europeo di Oncologia (IEO)	Milan
Italy	University of Eastern Piedmont	Novara
Italy	Salvatore Maugeri Foundation - Medical Oncology Unit	Pavia
Italy	Ospedale di Prato	Prato	Firenze
Italy	UO Oncologia, Rimini Hospital	Rimini
Italy	Regina Elena National Cancer Institute	Rome
Italy	Ospedale di Trento	Trento
Italy	AO Universitaria Ospedale Di Circolo e Fondazione	Varese
Italy	Ospedale Belcolle di Viterbo	Viterbo
Japan	Kansai Rosai Hospital	Amagasaki	Hyogo
Japan	NHO Kyushu Cancer Centre, 3-1-1 Notame Minami-ku Fukuoka-shi	Fukuoka
Japan	Seirei Hamamatsu General Hospital	Hamamatsu	Shizuoka
Japan	Social Medical Corporation Hakuaikai Sagara Hospital	Kagoshima
Japan	St Marianna University School of Medicine Hospital	Kawasaki
Japan	Kyoto University Hospital	Kyoto
Japan	NHO Shikoku Cancer Center	Matsuyama
Japan	Toranomon Hospital	Minato-ku, Tokyo
Japan	Kamiiida Daiichi General Hospital	Nagoya
Japan	Okayama University Hospital	Okayama
Japan	NHO Osaka National Hospital	Osaka
Japan	Tohoku University Hospital	Sendai
Japan	National Cancer Center for Global Medicine	Tokyo
Japan	National Cancer Center Hospital	Tokyo
Japan	Showa University Hospital	Tokyo
Japan	St Luke's International Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	University of Tsukuba	Tsukuba
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Lebanon	American University of Beirut Medical Center	Beirut
Netherlands	Leiden University Medical Centre, Albinusdreef 2, Postbus 9600	Leiden
Norway	Norwegian Radium Hospital (Oslo University)	Oslo
Portugal	Champalimaud Cancer Center - Breast Cancer Unit	Lisbon
Serbia	Institute of Oncology & Radiology of Serbia	Belgrade
Slovenia	Institute of Oncology Ljubljana - Medical Oncology Department	Ljubljana
Spain	Hospital General de Catalunya	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario Donostia	Donostia
Spain	Hospital Clinico Universitario Virgen de la Arrixaca	El Palmar	Murcia
Spain	Instituto Catalán de Oncología de Gerona Hospital	Gerona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario de Fuenlabrada	Madrid
Spain	Hospital Universitario HM Sanchinarro - Centro Integral Oncologico Clara Campal (CIOCC)	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Hospital Son Espases, Palma de Mallorca	Palma
Spain	Complejo Hospitalario de Navarra	Pamplona
Spain	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela
Spain	Hospital Quiron Sagrado Corazon	Sevilla
Spain	Universitario Virgen del Rocio	Sevilla
Spain	Hospital Virgen De La Salud	Toledo
Spain	Hospital General Universitario de Valencia - Servico Oncologia	Valencia
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
Switzerland	Kantonspital Baden AG	Baden
Switzerland	Universitätsspital Basel	Basel
Switzerland	Istituto Oncologico della Svizzera Italiana (IOSI)	Bellinzona
Switzerland	Inselspital Bern	Bern
Switzerland	Oncocare Bern	Bern
Switzerland	Brustzentrum Thurgau - Obstetrics and Gynecology	Frauenfeld
Switzerland	University Hospital Geneva	Genève
Switzerland	University Hospital of Lausanne (CHUV) BH06 - Oncology Department	Lausanne
Switzerland	CHCVs Hôpital de Sion - Service d'oncologie ambulatoire	Sion
Switzerland	Brustzentum Kantonsspital St. Gallen	St. Gallen
Switzerland	Spital STS AG Onkologiezentrum Thun-Berner Oberland	Thun	Bern
Switzerland	University Hospital Zurich	Zurich
Switzerland	Brust-Zentrum AG	Zürich
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	University of Colorado Cancer Centre - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Greater Baltimore Medical Centre	Baltimore	Maryland
United States	Johns Hopkins University	Baltimore	Maryland
United States	Sanford Clinic North - Bemidji	Bemidji	Minnesota
United States	Sanford Bismark Medical Centre	Bismarck	North Dakota
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Rocky Mountain Cancer Center	Boulder	Colorado
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	IHA Hematology Consultants-Brighton	Brighton	Michigan
United States	Saint Joseph Mercy Hospital - Brighton	Brighton	Michigan
United States	Montefiore Medical Center - Einstein Campus, 1695 Eastchester Road	Bronx	New York
United States	Montefiore Medical Center - Moses Campus, 111 East 210th Street	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	University of Vermont Medical Centre	Burlington	Vermont
United States	IHA Hematology Consultants-Canton	Canton	Michigan
United States	Saint Joseph Mercy Hospital- Canton	Canton	Michigan
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	IHA Hematology Consultants-Chelsea	Chelsea	Michigan
United States	Saint Joseph Mercy Hospital - Chelsea	Chelsea	Michigan
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	Southeastern Medical Oncology Centre	Clinton	North Carolina
United States	Ohio State University	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Carle on Vermilion	Danville	Illinois
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Carle Physician Group - Effingham	Effingham	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Northwestern University	Evanston	Illinois
United States	Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut
United States	Sanford Medical Centre	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Centre	Fargo	North Dakota
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	NorthShore University Health System - Glenbrook Hospital	Glenview	Illinois
United States	Southeastern Medical Oncology Centre	Goldsboro	North Carolina
United States	Greenville Health System Cancer Institute-Butternut	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Greer	Greer	South Carolina
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	NorthShore Unversity Health System - Highland Park Hospital	Highland Park	Illinois
United States	OnCare Hawaii Inc - POB I	Honolulu	Hawaii
United States	OnCare Hawaii-Kuakini	Honolulu	Hawaii
United States	Queen's Medical Centre	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	Indiana University	Indianapolis	Indiana
United States	Southeastern Medical Oncology Centre	Jacksonville	North Carolina
United States	Doctor's Hospital of Laredo	Laredo	Texas
United States	Dartmouth Hitchcock Medical Center/Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	Cedars Sinai Medical Centre	Los Angeles	California
United States	St John's Hospital	Maplewood	Minnesota
United States	Mattoon Charleston Primary Care	Mattoon	Illinois
United States	Bon Secours Memorial Regional Medical Centre	Mechanicsville	Virginia
United States	Bon Secours Saint Francis Medical Centre	Midlothian	Virginia
United States	Abbott-Northwestern Hospital, 800 East 28th Street	Minneapolis	Minnesota
United States	Hennepin County Medical Center - Cancer Center	Minneapolis	Minnesota
United States	Yale University - Yale Cancer Centre	New Haven	Connecticut
United States	Weill Medical College of Cornell University	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Helen F. Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newport	Delaware
United States	Regional Hematology Oncology Practice Associates	Newport	Delaware
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	Smilow Cancer Hospital-Orange Care Center	Orange	Connecticut
United States	Chagrin Highlands	Orange Village	Ohio
United States	Stanford Cancer Institute	Palo Alto	California
United States	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	Women and Infants Hospital of Rhode Island	Providence	Rhode Island
United States	Bon Secours Saint Mary's Hospital	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Park Nicollet Methodist Hospital	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	Huntsman Cancer Institute / University of Utah	Salt Lake City	Utah
United States	Sharp Memorial Hospital	San Diego	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina
United States	Sanford Cancer Centre Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Centre - Sioux Falls	Sioux Falls	South Dakota
United States	NorthShore Medical Centre	Skokie	Illinois
United States	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Carle Cancer Centre	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut
United States	Dickstein Cancer Treatment Centre	White Plains	New York
United States	Southeastern Medical Oncology Centre	Wilson	North Carolina
United States	IHA Hematology Oncology Consultants-Ann Arbor	Ypsilanti	Michigan

Sponsors (4)

Lead Sponsor	Collaborator
ETOP IBCSG Partners Foundation	Alliance for Clinical Trials in Oncology, Breast International Group, Canadian Cancer Trials Group

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Denmark,  France,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Lebanon,  Netherlands,  Norway,  Portugal,  Serbia,  Slovenia,  Spain,  Switzerland, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Breast Cancer free interval (BCFI)	Kaplan-Meier Analysis	From enrollment until the first invasive BC event, assessed up to 14 years
Secondary	Information on Menstruation recovery and pattern	Menstrual diary	Up to 24 months after enrollment
Secondary	Pregnancy rate (determined by pregnancy test)	Pregnancy test	Up to 24 months after enrollment
Secondary	Pregnancy outcome	Labor and delivery Information, full term pregnancy, caesarean section, abortion, miscarriage, ectopic, stillbirth rates.	Up to 33 months after enrollment
Secondary	Offspring outcome	Collect information on preterm birth, low birth weight, births defects rates.	Up to 33 months after enrollment
Secondary	Breastfeeding pattern	Analysis of pattern e.g Duration, use of ipsilateral breast if previous breast conservation, side exclusivity	Up to 36 months after enrollment
Secondary	Use of assisted reproductive Technology (ART)	ART use will be tabulated	Up to 24 months after enrollment
Secondary	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