For years, the question of pregnancy after, or during treatment for, hormone receptor–positive breast cancer placed patients and their oncologists in an uncomfortable position. Endocrine therapy, prescribed for 5 years and increasingly for 10 years or longer in high-risk patients, is both a cornerstone of treatment and a formidable obstacle for young women who have not yet completed their families. The “clinical conundrum” has been real, the data limited, and the guidance largely cautious, says Ann Partridge, MD, Co-Founder and Director of the Program for Young Adults with Breast Cancer at Dana-Farber Cancer Institute, and Professor of Medicine and Interim Chair of Medical Oncology at Harvard Medical School.
Ann Partridge, MD
“Women have told me they feel their life is like a ball and chain when they learned of their diagnosis and that they have to wait 5 or, in the high-risk setting, maybe 10 years” to attempt pregnancy, she said. The POSITIVE trial was designed to determine whether premenopausal hormone receptor–positive patients could be safely treated for their cancer while pursuing family goals. Study results, first reported in 2023,1 were indeed positive and reassuring. They showed that a 2-year interruption of endocrine therapy often led to healthy pregnancies without compromising oncologic outcomes and were thus life-altering for many young patients with breast cancer.
Participants have now been followed for 5 years. The 71-month analysis validates the primary findings, providing rigorous and reassuring evidence that a carefully managed treatment pause is feasible, that live birth rates are high, and that survival outcomes are not compromised,2 according to Dr. Partridge, the study’s principal investigator, who described the recent analysis at the 43rd Annual Miami Breast Cancer Conference, sponsored by Physicians Education Resource.
Importance of the Study
The POSITIVE trial, led by the International Breast Cancer Study Group (IBCSG), enrolled 516 premenopausal women with hormone receptor–positive, HER2-negative early breast cancer who wanted to attempt pregnancy. The protocol required participants to complete 18 to 30 months of endocrine therapy before entering a washout period designed to eliminate teratogenic drug exposure. Women were then given up to 2 years to conceive, carry a pregnancy, deliver, and breastfeed if desired, before resuming treatment.
The enrolled population reflected the clinical reality of young breast cancer: the majority were nulliparous with a mean age of 37, ie, women for whom fertility concerns are acutely time-sensitive. Most had stage I or II disease (6% stage III), 40% were node-positive, and 62% had received chemotherapy. All standard endocrine therapy options were represented.
Fertility Outcomes: High Live Birth Rates, Complications Consistent With Population Norms
The updated analysis of the fertility outcomes challenges long-standing assumptions about the practical feasibility of pregnancy after breast cancer. “I was once on the dais with an IVF [in vitro fertilization] doctor who told the audience that women can’t get pregnant after breast cancer. He said that even if it was safe, it’s not feasible. I’m going to show you some data that suggest what he said is garbage,” Dr. Partridge told meeting attendees.
“What were the results at 71 months? The most important thing is that most women had a baby, and most had a live birth,” she said. Of the 497 evaluable patients, 377 (76%) reported becoming pregnant at least once, with a total of 589 pregnancies. The 440 live births included 18 sets of twins; 75 women had more than one live birth. Of the live births, 67% were full-term infants and 5% were preterm.
Obstetric complication rates were consistent with population norms for women of a similar age. Approximately 2.5% experienced pregnancy complications, 8.6% had low-birth-weight infants, and 1.8% had infants with birth defects—figures in line with baseline rates in Western countries for a relatively older maternal cohort, Dr. Partridge noted.
No Signal of Harm at 71 Months
The central concern animating the POSITIVE trial—whether temporary interruption of endocrine therapy would worsen oncologic outcomes—has not been borne out in the updated data. When POSITIVE participants were compared against a matched cohort from the SOFT and TEXT trials, controlling for tumor size, nodal status, and prior treatment, both breast cancer–free interval events and distant recurrence–free events were similar between women who paused therapy for pregnancy and those who did not.
For the POSITIVE participants and SOFT/TEXT participants, respectively, breast cancer–free interval events at 71 months were 12.3% and 13.2% (hazard ratio [HR] = 0.88); distant recurrence–free interval events were 6.2% and 8.3%, respectively (HR = 0.67), Dr. Partridge reported.
“Both breast cancer–free interval events as well as distant recurrence–free events were similar: no worsening in terms of how women did for those who went on POSITIVE compared to those who did not,” she said.
A landmark analysis embedded within the POSITIVE data, which Dr. Partridge highlighted as compelling, addressed whether pregnancy itself poses a recurrence risk. Among participants with no evidence of disease at enrollment, those who became pregnant within 18 months were compared to those who did not. This was essentially a head-to-head comparison of women who all wanted a pregnancy, differentiated only by whether they achieved it within the landmark window. The breast cancer–free interval was not statistically different between the two groups. In fact, the hazard ratio favored the pregnant group (HR = 0.64), she reported.
“That’s kind of the nail in the coffin that a pregnancy itself would actually cause a recurrence,” she maintained. “If anything, the people who had a pregnancy clearly had fewer recurrences, at least numerically.”
Assisted Reproductive Technology: Effective and Apparently Safe
Of the 497 evaluable patients, 214 (43%) used any assisted reproductive technology (ART) in the first 2 years on trial. Embryo transfer was associated with the chance of pregnancy more than doubling. Oncologic outcomes among ART users were comparable to those who did not require assisted reproduction. The findings confirm that ART functions as expected in this population and without apparent oncologic penalty, Dr. Partridge said.
A total of 17% percent of participants underwent ovarian stimulation during the trial itself, “without a smidge of evidence that that was harmful,” Dr. Partridge noted, though she acknowledged this analysis was uncontrolled and the trial was not powered to evaluate this endpoint definitively. Data on pretrial fertility preservation were similarly encouraging. Patients who had undergone ovarian stimulation prior to trial enrollment did no worse than those who had not, reinforcing the recommendation to discuss and facilitate fertility preservation at diagnosis for all premenopausal women with early-stage disease.
Endocrine Therapy Resumption and Risk Stratification
Adherence to endocrine therapy resumption after pregnancy was notably strong. At 71 months, 72% of POSITIVE participants had restarted treatment, which Dr. Partridge described as favorable against general population adherence data showing that roughly 50% of young patients discontinue endocrine therapy by 5 years. By the 2-year mark, 82% of eligible participants had resumed.
Recurrence predictors within the POSITIVE population tracked closely with established risk factors: nodal positivity, tumor size, and HER2 status. Among node-positive patients with four to nine involved nodes, the 71-month recurrence rate reached 23%, speaking to the persistence of underlying disease risk regardless of the pregnancy decision. High-risk node-positive disease, she commented, “is not a spectator sport… . There’s still this risk of recurrence, and pregnancy isn’t necessarily going to fix that.”
BRCA Carriers, Broader Data, and Financial Barriers
The presentation also reviewed data from a matched analysis examining pregnancy outcomes in 4732 BRCA mutation carriers under the age of 40, drawn from a worldwide collaboration.3 One in five young carriers conceived within 10 years of breast cancer diagnosis, and their pregnancy was not associated with decreased disease-free survival across both matched and extended Cox model analyses. Women with estrogen receptor–negative disease were more likely to pursue pregnancy, likely reflecting reduced concerns about endocrine therapy interruption in that subgroup, she reported.
In closing, Dr. Partridge concluded that the updated POSITIVE data provide a prospective, trial-level evidence base for counseling patients in a domain in which only retrospective registry data had previously existed, along with a degree of reassurance that a time-limited, protocol-driven pause does not carry the oncologic penalties that had long been feared. She cautioned, however, that the results should not be read as a blanket endorsement of treatment interruption across all patients.
“Updated data from POSITIVE and other studies support the feasibility and safety of pregnancy and assisted reproductive technologies in our survivor populations, carefully and thoughtfully,” she commented. “We just really need to support our patients as they make these decisions.”
DISCLOSURE: Dr. Partridge had no relevant disclosures.
REFERENCES
1. Partridge AH, Niman SM, Ruggeri M, et al: Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 388;1645-1656, 2023.
2. Peccatori FA, Pagani O, Niman SM, et al: POSITIVE trial investigators. Temporary interruption of adjuvant endocrine therapy for pregnancy in women with hormone receptor–positive early breast cancer: Updated outcomes. 2025 ESMO Congress, Abstract LBA12. Presented October 17, 2025.
3. Lambertini M, Blondeaux E, Agostinetto E, et al: Pregnancy after breast cancer in young BRCA carriers: an international hospital-based cohort study. JAMA 331(1):49-59, 2024.
