Pregnancy Outcome and Safety of Interrupting Therapy for women with endocrine responsIVE breast cancer (POSITIVE).
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.
- 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.
- 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 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
- 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.
- 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
- 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
- Patients with a history of noncompliance to medical treatments and/or considered
- Patients with psychiatric, addictive, or any disorder that would prevent compliance
with protocol requirements.