Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2026 Aug 25.
Published in final edited form as: Ann Oncol. 2026 May 28;37(9):1230–1241. doi: 10.1016/j.annonc.2026.05.699

Updated Results of the POSITIVE (Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine Responsive Breast Cancer) Trial

Olivia Pagani 1,2,3, Samuel M Niman 4,5, Monica Ruggeri 6, Fedro A Peccatori 7, Hatem A Azim Jr 8, Marco Colleoni 9, Cristina Saura 10,11, Chikako Shimizu 12, Anna Barbro Sætersdal 13, Judith R Kroep 14,15, Ellen Warner 16, Frédéric Amant 17,18,19, Audrey Mailliez 20, Halle CF Moore 21, Manuel Ruiz-Borrego 22,23, Janice M Walshe 24,25, Virginia F Borges 26, Andrea Gombos 27, Akemi Kataoka 28, Christine Rousset-Jablonski 29,30,31, Simona Borstnar 32,33, Junko Takei 34, Jeong Eon Lee 35,36, Christobel Saunders 37,38, Vesna Bjelic-Radisic 39,40, Snezana Susnjar 41, Fatima Cardoso 42, Natalie J Klar 43, Teresa Ferreiro 44, Karin Ribi 45,46, Kathryn J Ruddy 47, Roswitha Kammler 48, Sarra El-Abed 49, Giuseppe Viale 50,51, Martine Piccart 27,49, Larissa A Korde 52, Aron Goldhirsch 53,54, Richard D Gelber 4,5,55,56,58, Ann H Partridge 57,58, for the International Breast Cancer Study Group and the POSITIVE Trial Consortium
PMCID: PMC13501236  NIHMSID: NIHMS2198591  PMID: 42214557

Abstract

Background:

In patients with hormone receptor-positive (HR+) early breast cancer (BC), the POSITIVE trial demonstrated that temporary interruption of adjuvant endocrine therapy (ET) for pregnancy is feasible and safe in early follow-up (median 41 months). Here we report updated results from a pre-planned analysis with 2.5 years of additional follow-up.

Patients and methods:

POSITIVE, a single-arm prospective trial evaluating temporary interruption of adjuvant ET (after 18–30 months and for up to 2 years) to attempt pregnancy in young BC patients, enrolled 518 eligible women (≤42 years of age, stage I-III BC, desiring pregnancy) from 12/2014 to 12/2019. Using the bootstrap-matching method, 5-year breast cancer-free interval (BCFI) and distant recurrence-free interval (DRFI) event rates are compared to those of SOFT/TEXT trials as external controls.

Results:

At a median follow-up of 71 months in the POSITIVE cohort and 80 months in the SOFT/TEXT cohort, the 5-year cumulative incidence of BCFI events was 12.3% in POSITIVE and 13.2% in SOFT/TEXT (-0.9% difference, 95% CI −4.2% to 2.6%). The 5-year cumulative incidence of DRFI events was 6.2% and 8.3%, respectively, (-2.1% difference, 95% CI −4.5% to 0.4%). Among 497 women followed for non-disease outcomes, 377 (76%) had ≥1 documented pregnancy on trial, 343/497 (69%) had ≥1 live birth, with 440 offspring. In an unadjusted analysis comparing the 180 women (36%) who had pre-enrollment embryo/oocyte cryopreservation to those who did not, the 5-year cumulative incidence of BCFI events was 14.0% (95% CI: 9.6% to 20.2%) and 11.5% (95% CI: 8.4% to 15.7%), respectively.

Conclusion:

Longer-term follow-up of the POSITIVE trial demonstrates that temporary interruption of ET for pregnancy including use of fertility preservation does not increase risk of BC events. Continued follow-up is warranted given the known risk of late recurrence in this population.

Keywords: breast cancer, pregnancy, endocrine therapy interruption, young women

Introduction

Breast cancer (BC) is the most common cancer in young women, with incidence increasing worldwide.1, 2 Compared with older women, the disease and associated treatment can be profoundly disruptive adding greater medical and psychosocial morbidity in both short- and long-term survivorship,3 with the feasibility and safety of subsequent pregnancy representing major concerns.4–6 For women with early-stage hormone receptor-positive (HR+) BC, fear that pregnancy might increase risk of recurrence has limited pregnancy considerations after BC, despite retrospective evidence to the contrary.7, 8 Further, pregnancy is contraindicated during adjuvant endocrine therapy (ET), and aging during ET and prior chemotherapy substantially reduce the chances of a future successful conception.9, 10 Given the hazards of relapse in HR+ BC persist for many years, delaying pregnancy to pass a specific period of risk may be unwarranted.11

The prospective single arm POSITIVE trial [ClinicalTrials.gov, NCT02308085] was designed to address this clinical conundrum by evaluating temporary interruption of adjuvant ET for pregnancy in young women with prior HR+ BC.12, 13 The primary endpoint was breast-cancer-free interval (BCFI) (time from enrollment to first BC event), with planned analysis after 1600 patient-years follow-up, and ≤46 BC events as the prespecified safety threshold. As previously reported, after 1638 patient-years follow-up (median 41 months), 44 participants experienced a BC event, not exceeding the safety threshold.14 The 3-year BC event percentage was 8.9% (95% CI: 6.3 to 11.6%), compared to 9.2% (95% CI: 7.6 to 10.8%) for an external control group, demonstrating that pregnancy did not increase short-term risk of BC events, including for participants who used assisted reproductive technologies (ART) after breast cancer.15 Here, we present updated results of the POSITIVE trial.15

Patients & Methods

As previously described, POSITIVE is a prospective, multicentre, multinational, investigator-initiated single-arm clinical trial with planned enrolment of 500 patients ≤42 years with stage I-III, HR+ BC, who had received adjuvant ET (SERM alone, GnRH analogue plus SERM or aromatase inhibitor (AI)) for 18–30 months and wished to interrupt therapy to attempt pregnancy.14 The protocol stipulated up to 2 years interruption of ET for pregnancy attempt (including a 3-month ET washout period), conception (or failure to conceive), delivery, and breastfeeding if desired and feasible after which ET resumption was strongly recommended to complete 5–10 years of treatment. ART was allowed. Data on disease outcomes, ART use, pregnancy, offspring outcomes and patterns of breastfeeding were collected.

The study, a worldwide collaborative partnership of several research groups (see appendix) coordinated by the International Breast Cancer Study Group (IBCSG), recruited patients in 116 centers across 20 countries on 4 continents. Three prespecified interim analyses were conducted under the auspices of the Independent Data Monitoring Committee (IDMC), who made recommendations to the investigators, who vouch for the completeness and accuracy of the data and analyses and for the fidelity of the trial to the protocol. The current analysis represents a pre-planned analysis with data cut-off 2.5 years after the data cut-off for the primary analysis.14 The first draft of this manuscript was written by the last author and study statisticians. All authors contributed to subsequent drafts and no others contributed to the writing. The trial was conducted in accordance with the amended Declaration of Helsinki, and the protocol was approved by the institutional-review-board at each participating center. All patients provided written informed consent.

Treatment & Assessments

Patients were enrolled within one month of discontinuing ET, with required 3-months washout prior to attempting pregnancy (Supplementary Figure S1, POSITIVE SCHEMA). Suspension of ET could be up to 2 years to allow attempting pregnancy, conception, delivery, and breast feeding. Following enrolment, medical history (including pregnancy and ET use) and clinical assessments were performed according to institutional standards on a 6-month basis for 5 years and annually thereafter up to 10 years.

Statistical Analysis

The primary endpoint of BCFI was defined as the time from study enrolment until the date of first occurrence of one of invasive local, regional, or distant recurrence or contralateral invasive BC.16 Patients without a documented BC event were censored at the date they were last known to be disease free. Distant recurrence free interval (DRFI) was defined as the time from study enrolment until the date of first invasive distant recurrence. Patients without a documented DRFI event were censored at the date they were last known to be invasive distant recurrence free.

Analyses regarding the safety of interrupting ET follow the intention-to-treat principle (ITT), with 516 out of 518 enrolled participants comprising the primary efficacy analysis population (Figure 1, Flow Diagram). Median follow-up was estimated from the censoring distribution of overall survival using the inverse Kaplan-Meier method. The primary evaluation of the safety of suspending ET to pursue pregnancy was done by comparing the cumulative incidence rate (1-Kaplan-Meier) of BCFI events at 5-years between POSITIVE and an external control cohort of 1499 patients from the SOFT/TEXT trials17 that met the eligibility criteria for POSITIVE including time since diagnosis.18 Bootstrapping methods were used to generate 5000 samples of both cohorts and estimates of the 5-year cumulative incidence of BCFI events were generated for both cohorts in each sample; the difference in 5-year estimates between the two cohorts was also estimated for each of the 5000 samples.14, 18 The 2.5 and 97.5 percentiles of the distribution of the 5000 estimates were used for the 95% confidence intervals. Additionally, a stratified Cox proportional-hazards model was used to estimate the hazard ratio and confidence intervals; note that model featured the non-bootstrapped populations of POSITIVE and the SOFT/TEXT control cohort. Given that treatment outcomes for HER2+ BC have improved substantially since the SOFT/TEXT recruitment period,19 a subgroup analysis was conducted amongst patients with HER2- disease. The bootstrap sampling was repeated to only include participants with HER2- disease in both cohorts. Methods of estimation and comparison for the HER2- cohort mirrored those for the overall cohort.

Figure 1:

Figure 1:

Open in a new tab

Flow Diagram

To evaluate the potential impact of on-trial exposures on outcomes, additional secondary analyses were conducted. To explore the relationship between pregnancy and BCFI two separate methods were utilized: 1) A landmark analysis was used to estimate the cumulative incidence of BCFI events by on-trial pregnancy status. 2) A time-dependent multivariable Cox proportional hazards model, with covariates including age, BMI, lymph node status, prior chemotherapy, AI treatment, and time-varying on-trial pregnancy status, was used to estimate the hazard ratio of BCFI for patients who had an on-trial pregnancy vs those who did not.

The relationship between ovarian stimulation (pretrial and, separately, on trial) and BCFI was examined. Kaplan-Meier methods were used to estimate the cumulative incidence of BCFI events by pretrial ovarian stimulation status. In addition, a landmark analysis was used to estimate the cumulative incidence of BCFI by on-trial use of ovarian stimulation as part of ART.

To determine the rate of first pregnancy, a competing risks analysis was used to estimate the cumulative incidence of first pregnancy in the presence of competing risks including: cancer events, ET resumption, and no longer attempting pregnancy. To explore patient, and treatment characteristics associated with pregnancy, logistic regression was used. The model included age at enrollment, prior pregnancy, use of ART, use of GnRH through chemotherapy, HER2 status, and duration of prior ET. To determine the rate of ET resumption the cumulative incidence of ET was estimated in the presence of competing risks including cancer events and death without cancer events.

Secondary endpoint analyses are considered exploratory in nature, due to the multiplicity of such analyses and only the 497 patients that had some post enrollment follow-up were included in the secondary endpoint population. Note that all secondary endpoint analyses feature patients from the POSITIVE trial and do not include the SOFT/TEXT cohort.

Results

Between December 2014 and December 2019, 518 women were enrolled in the study, among whom 516 comprised the evaluable population (Figure 1). Median age at enrolment was 37 years (range 27–43), 75% had no prior live births, and most had stage I or II BC (93%) (Table 1). Median duration of ET received prior to enrolment was 23.4 months, 58% received ovarian function suppression, and 62% had received chemotherapy.

Table 1:

Patient, disease, and treatment characteristics of POSITIVE patients

Total
N %
Primary efficacy analysis population patients 516 100.0
Age group - yr
 <35 177 34.3
 35–39 221 42.8
 40–42 118 22.9
Race
 White 397 76.9
 Black 7 1.4
 Asian 90 17.4
 Other/Unknown 22 4.3
Body-mass index
 <25 371 71.9
 ≥25 139 26.9
 Unknown 6 1.2
Previous births
 None 387 75.0
 At least one 129 25.0
BRCA status
 BRCA1 positive 18 3.5
 BRCA2 positive 20 3.9
 Other mutation 21 4.1
 Negative 207 40.1
 Not tested 233 45.2
 Results not shared 16 3.1
 Unknown 1 0.2
Tumor size - cm
 ≤2cm 331 64.1
 >2cm/≤5cm 161 31.2
 >5cm 21 4.1
 Unknown 3 0.6
No. positive lymph nodes
 0 342 66.3
 1–3 151 29.3
 4–9 23 4.5
Tumor histological grade
 1 89 17.2
 2 252 48.8
 3 172 33.3
 Unknown 3 0.6
HER2 status
 Positive 134 26.0
 Negative 382 74.0
Adjuvant endocrine therapy
 SERM alone 215 41.7
 SERM and OFS 184 35.7
 AI and OFS 82 15.9
 Other 35 6.8
Previous neoadjuvant or adjuvant chemotherapy
 Yes 320 62.0
 No 196 38.0
Open in a new tab

Breast Cancer Events and Distant Recurrences

With a median follow-up of 71 months (5.9 years) and 80 months (6.6 years) in the POSITIVE and SOFT/TEXT control cohorts, respectively, the cumulative incidence of BCFI events at 5 years was 12.3% (95% CI: 9.4% to 15.2%) in POSITIVE compared to 13.2% (95% CI: 11.4% to 15.1%) in SOFT/TEXT, with a difference in the 5-year cumulative incidence of BCFI events between the two cohorts of −0.9% (95% CI: −4.2% to 2.6%) (Figure 2a). Approximately half of events were distant recurrences, and the difference in the 5-year cumulative incidence of DRFI events was −2.1% (95% CI: −4.5% to 0.4%) (Figure 2b).

Figure 2:

Figure 2:

Open in a new tab

Cumulative incidence of BCFI (a) and DRFI (b) events, as estimated by the bootstrapped matching method (BMM), for both the POSITIVE cohort and the SOFT/TEXT external control cohort

Sensitivity Analysis of Participants with HER2-negative Disease

The sensitivity analysis included the 382 participants with HER2-negative BC in POSITIVE compared to 1192 women with HER2-negative BC in SOFT/TEXT. The cumulative incidence of BCFI events at 5 years was 14.1% (95%CI: 10.5% to 17.8%) in POSITIVE compared to 13.1% (95% CI: 11.0% to 15.2%) in SOFT/TEXT, with a difference of 1.0% (95% CI: −3.2% to 5.2%) (Supplementary Figure S2a). For DRFI, 5-year cumulative incidence of events was 6.8% (95% CI: 4.2% to 9.5%) for POSITIVE patients, and 7.9% (95% CI: 6.3% to 9.6%) for SOFT/TEXT with an absolute difference between the two cohorts of −1.1% (95% CI: −4.0% to 1.9%) (Supplementary Figure S2b).

Subgroup, Landmark and Time-dependent Cox Analyses in the POSITIVE Cohort Only

Evaluation of prognostic subgroups of POSITIVE participants revealed expected relationships between disease characteristics and higher risk of recurrence, e.g. increasing nodal burden, tumor size, and tumor grade (Figure 3). HER2-positivity was associated with numerically lower risk of 5-year BCFI events.

Figure 3:

Figure 3:

Open in a new tab

Forest plot of 5-year cumulative incidence of BCFI events percentage by subgroup - POSITIVE cohort only

A landmark analysis including the 456 patients who were disease-free for at least 18 months compared the 137 (30%) participants who did not report a pregnancy to the 305 (67%) who reported at least one pregnancy by 18 months. The cumulative incidence of BCFI events at 42 months post landmark (5 years from enrollment) was 6.7% among those who got pregnant by 18 months compared to 7.6% among those without a pregnancy by 18 months (Figure 4). Multivariable time-dependent adjusted Cox model confirmed no evidence that pregnancy increased risk of a BC event in the POSITIVE cohort with BCFI hazard ratio (pregnant vs. not pregnant) of 0.65 (95% CI: 0.37 to 1.14) (Supplementary Table S3).

FIGURE 4:

FIGURE 4:

Open in a new tab

18-Month landmark cumulative incidence curves of BCFI events according to pregnancy status (no/yes) at 18 months for the 456 patients that had at least 18 months of follow-up without a BC event or second malignancy

ART and Breast Cancer Outcomes

Among 497 participants in POSITIVE followed for ART use and outcomes, at 5 years, the cumulative incidences of BCFI events among the 180 (36%) who had ovarian stimulation and embryo/oocyte cryopreservation prior to enrolment and those who did not was 14.0% (95% CI: 9.6% to 20.2%) and 11.5% (95% CI: 8.4% to 15.7%), respectively (Supplementary Figure S3). Among 438 patients that were alive and in follow-up 2 years after enrollment, 74 (16.9%) used ovarian stimulation on trial. A 2-year landmark analysis demonstrated that the cumulative incidence of a BFCI event 3 years beyond the landmark was 8.3% (95% CI: 3.8% to 17.5%) in those who underwent ovarian stimulation on trial and 5.3% (95% CI: 3.4% to 8.2%) in those who did not (Supplementary Figure S4).

Pregnancy Outcomes

Among the 497 women followed for pregnancy outcomes, 377 (75.9%) had at least one documented pregnancy on trial, with a total of 589 pregnancies at the time of database lock. Accounting for the competing risks of cancer events, ET resumption, and discontinuation of pregnancy attempts, the cumulative incidence of pregnancy was 28.8% (95% CI: 24.9–32.8%) at 6 months after enrolment, 53.4% (95% CI: 48.9–57.7%) at 12 months, 70.3% (95% CI: 66.0–74.2%) at 24 months, and 76.0% (95% CI: 71.8–79.6%) at 48 months (Supplementary Figure S5). The longest time from enrollment to first pregnancy was ~47 months in this updated analysis.

A logistic regression model to identify patient, disease, and treatment characteristics associated with pregnancy (Supplementary Table S1) revealed that only younger age at enrollment and use of ART were significantly associated with higher pregnancy incidence (Supplementary Table S2).

The number of POSITIVE participants with at least one live birth was 343/497 (69%), representing 91% (343/377) of those who had at least one pregnancy on trial. There were 422 pregnancies with live births and 440 live offspring (18 sets of twins). Seventy-five patients had more than 1 pregnancy leading to live birth (including 4 patients who had at least 3 live birth pregnancies).

Of the 589 total pregnancies, 392 (66.6%) resulted in full term and 30 (5.1%) in preterm live births, and there were 129 (21.9%) miscarriages, 2 (0.3%) stillbirths, 24 (4.1%) elective abortions, 4 (0.7%) active pregnancies, and 8 pregnancies with unknown outcomes (1.4%). The most frequent complication of pregnancy was hypertension (2.5%). Of the 440 offspring, 8.6% had low birth weight, and 1.8% had birth defects.

Resumption of ET

Among the 429 patients that had at least 2 years of disease-free follow-up, 352 (82.1%) resumed ET at some point following the initial interruption (Supplementary Table S4). Of the 77 disease-free patients who had not yet resumed ET, 27 (35.1%) were pregnant, pursuing pregnancy, or breastfeeding, 26 (33.8%) declined to restart ET, and 24 (31.2%) had some other reason for not resuming.

Supplementary Figure S6 details the cumulative incidence of ET resumption over time, accounting for competing risks of cancer events (BC and other malignancy), and death without recurrence demonstrating cumulative incidence of ET resumption was 34.7% at 24 months, 59.0% at 30 months, 67.4% at 36 months, and 73.8% at 48 months. The cumulative incidence of ET resumption reached 50% at 27 months. In terms of competing events, at 48 months 9.2% had disease events prior to resuming ET and 0.2% died prior to having a disease event or resuming ET.

Discussion

Given most young women retain fertility after BC treatment, a substantial proportion of survivors desire subsequent pregnancy, and many become pregnant,20–22 improved understanding of the potential effects of subsequent pregnancy on BC outcomes is critical for this population. Longer-term follow-up of the POSITIVE trial demonstrates that temporary interruption of ET for pregnancy including use of fertility preservation does not increase risk of BC events. This is encouraging for the increasing number of young BC patients and survivors who have not completed their reproductive plans.12, 23–25 Considering the complex relationship between BC and pregnancy, with pregnancy transiently increasing a woman’s risk of developing BC,26 there have long been concerns that pregnancy after early BC might increase the risk of BC recurrence and reduce survival, particularly in the setting of HR+ disease.27 Despite abundant retrospective data as well as the initial early results of the POSITIVE trial revealing no clear detriment to maternal BC outcomes, apprehensions remain particularly about the need for longer-term data.7, 14, 28

Prior to the POSITIVE Trial, the best available data suggested no clear worsening of survival in BC survivors who have become pregnant or had a live birth, compared with those who have not.7, 22 In a meta-analysis including over 112,000 patients with history of BC, 7,505 of whom had a subsequent pregnancy, those who became pregnant had better disease-free survival (HR 0.66, 95% CI 0.49–0.89) and overall survival (HR 0.56, 95% CI 0.45–0.68) compared with those who did not, even when correcting for potential confounders.7 A more recent analysis confirmed these findings in a national cohort of Scottish women with BC diagnosed at age 20–39 years between 1981 and 2017 (n = 5181), using national registries for cancer diagnosis and maternity records. Overall survival was better in 290 women with a live birth after diagnosis compared to a matched group who did not have a subsequent live birth (n = 1682) (HR 0.65 (95%CI 0.50–0.85)), regardless of hormone receptor status or receipt of chemotherapy. Women with subsequent live birth who had not had a pregnancy before BC showed greater survival (HR 0.56, 0.38–0.82), with a progressively stronger relationship for younger women (20–25 years) [HR 0.30 (0.12–0.74) vs. older women (36–39 years) [HR 0.89 (0.42–1.87)]. In women who had a live birth within five years of diagnosis, survival was also better (HR 0.66; 0.49–0.89). In contrast, in a well-controlled multicenter, retrospective cohort study in which patients who became pregnant any time after BC (n=333) were matched (1:3) to patients with BC with similar hormone receptor and nodal status, adjuvant therapy, age, and year of diagnosis (n=874), no difference in disease-free survival was observed between pregnant and non-pregnant patients in the HR+ population.29 In the same analysis, no difference in disease-free survival was observed between patients who became pregnant within two years following BC diagnosis and those who became pregnant afterwards.29

Prior evidence has been hampered by several limitations including the “healthy mother” bias, i.e., that healthy BC survivors are more likely to become pregnant than unhealthy, higher risk or ill survivors.30 These studies have also suffered from a lack of statistical power of the retrospective studies and often insufficient information in the HR+ disease patient populations, as well as heterogeneity of and uncertainty about the timing of pregnancy after BC including unknown disease status at the time of pregnancy.

The POSITIVE trial, as the first prospective study to enroll only women with HR+ disease who desired pregnancy, attempts to overcome these limitations. The trial not only assesses the general safety of pregnancy after BC, but also a pragmatically timed interruption of ET to optimize family planning goals. The overall finding that the risk of BC, including distant recurrence, is not increased in women who temporarily interrupt ET after at least 18–30 months to pursue pregnancy has important implications. Findings from POSITIVE suggest that while ET improves both disease-free and overall survival in patients with early HR+ BC,31–33 temporary breaks in therapy in particular settings, such as for pregnancy, may not negatively impact on disease outcomes. Findings may also provide new insights into tumor biology and dormancy. Pauses in ET have been tested prospectively among post-menopausal women on extended duration AI therapy in the SOLE trial, where 3-month treatment interruptions every 9 months over a five-year period did not compromise disease-free survival, and was associated with better quality of life than continuous administration.34, 35 It is also possible that pregnancy (and associated lactation) confers a protective effect on risk of recurrence, opposing a potential negative impact of the ET break, which has been documented to be particularly detrimental in young patients.36 Pregnancy causes wide-ranging physiological changes, including shifts in the hormonal and immune environments.37 These changes might play a role in preventing cancer recurrence, although more research is needed.38 While neither interruption of ET for pregnancy nor pregnancy itself appeared to increase risk of recurrence in POSITIVE compared with SOFT/TEXT external controls, women with history of early breast cancer with higher risk features (high nodal burden, larger tumor size, and high tumor grade) have, as expected, increased risk of recurrence, and those with HER2-positive disease experience fewer breast cancer events.

Nearly three-quarters of the women in the POSITIVE trial achieved at least one pregnancy, most (70%) within 2 years of enrollment, demonstrating the feasibility of pregnancy in BC survivors. As previously reported at 41 month median follow-up, factors associated with pregnancy in longer-term follow-up were consistent with those in the literature in the general population including younger age and use of ART.15, 39, 40 The relatively high use of ART in this population (over 40% while on trial) is likely attributable to many factors including the older age of participants, the imperative to become pregnant quickly given the relatively narrow window stipulated per protocol for endocrine therapy interruption, the desire to use oocytes/embryos banked at a younger age and prior to gonadotoxic treatment, as well as to utilize pre-implantation genetic diagnosis in the setting of a known hereditary predisposition to disease.41 Most women who used ART reported having banked eggs or embryos prior to systemic treatment, the current standard of care for fertility preservation.42, 43 However our landmark analysis finding that use of ovarian stimulation on trial does not appear to confer increased risk is reassuring for those who need it to achieve pregnancy during the ET interruption.

The relatively high rate of women having at least one successful pregnancy (i.e., having a live birth) in the POSITIVE trial contrasts with fertility rates in the general population among women of similar age, suggesting the high motivation of these women to become pregnant and is likely also related to the relatively high use of ART.44–46 Birth outcomes were also similar to that of the general population,47, 48 though increased risks of delivery complications, cesarean section, preterm birth and low birth weight were reported in one large study.48 More recent data, however, suggest that timing of pregnancy after diagnosis and treatment is a critical component of fetal outcome; women who conceive at least 1 year after starting chemotherapy do not appear to have a higher risk of preterm birth.49 In POSITIVE, the requirement of at least 18 months of ET prior to enrollment likely mitigated potential increased risk of fetal or peripartum complications from earlier chemotherapy and/radiation. Endocrine agents disturb the hormonal environment, and should be avoided during pregnancy.50 Thus, POSITIVE required a 3-month washout period after interruption before attempting conception, taking into account SERMs and AIs median half-lives. Our finding a low incidence of birth defects, not clearly associated with a treatment exposure, and consistent with that of an older non-cancer maternal population demonstrates the safety of this approach.1, 51 POSITIVE enrolled prior to the now standard adjuvant use of immunotherapy, CDK 4/6 inhibitors, and Olaparib in specific populations, and future research will have to address their impact on the safe timing of pregnancy, fertility rates, and feasibility of pregnancy after these newer treatments for women with higher risk disease.

In designing the trial, there was concern that women would not resume ET, however on-trial rates of refusal to resume ET, to date, appear to be consistent with non-persistence rates in young patients in prior clinical trials and real world studies.52–55 In a prospective cohort of 288 women within the ELIPPSE40 study, 29.7% of women age <40 had discontinued tamoxifen after 2 years, and the proportion increased to 39.5% after 3 years from start.55 However, recent data from real-world adoption of the POSITIVE approach to pregnancy after BC raise concern about higher rates of ET non-resumption and make it imperative that oncologists emphasize with patients the importance of ET resumption to optimize disease outcomes.56 Future analyses will explore the impact of longer interruptions than the protocol-specified up to 2 years.

These updated results of POSITIVE should be considered in the context of some limitations. While this report details 71-month median follow-up data, longer-term follow-up of these patients is critical given the decades-long trajectory of risk with HR+ BC; follow-up of each patient enrolled in POSITIVE is planned for ten years.57, 58 While a prospective, randomized trial would have been the best method to assess the safety of interrupting ET for pregnancy in young BC survivors, such a study design was not feasible.12, 14

The POSITIVE trial, with a conservative design including early stopping rules and an innovative external control group calculated from the large SOFT/TEXT clinical trials, demonstrates in longer-term follow-up that there is no clear worsening of BC outcomes associated with interrupting ET for subsequent pregnancy in women with a history of HR+ BC who desire pregnancy. These findings provide reassurance for individual patients, their partners and caregivers weighing pros and cons of pregnancy after early BC. Many questions remain, such as safety of having a second child during another ET interruption, and further follow up is clearly warranted.

Supplementary Material

Author accepted suppl file

Highlights.

  • Interruption of endocrine therapy for pregnancy does not increase breast cancer events in longer-term follow-up

  • History of ovarian stimulation and embryo/oocyte cryopreservation was not associated with higher risk of breast cancer events

  • Most women enrolling in the POSITIVE trial became pregnant and predictors of pregnancy included history of ovarian stimulation for cryopreservation before or during the trial and younger age

Acknowledgement

The POSITIVE trial was initiated by the Breast International Group (BIG) and the North American Breast Cancer Group (NABCG) Endocrine Working Group. The International Breast Cancer Study Group (IBCSG), the trial sponsor and coordinating group, was responsible to design and conduct the trial in collaboration with BIG's affiliated cooperative groups and the Alliance for Clinical Trials in Oncology (the North American sponsor), including the National Cancer Institute of the National Clinical Trials Network, and others.

We would like to express our sincere gratitude to the patients and their families; the aforementioned trial partners; the supporters, including all national funding bodies, charities, and private donors; the collaborators; and the current and former members of the trial's committees and investigators.

Funding

The POSITIVE trial is supported by the ETOP IBCSG Partners Foundation (globally) and the Alliance for Clinical Trials in Oncology (in North America), in collaboration with the Breast International Group (BIG), the BIG cooperative groups, and the National Clinical Trials Network of the US National Cancer Institute.

Globally, the trial receives grant support for central or local trial conduct from the following: the International Breast Cancer Study Group (IBCSG), Frontier Science and Technology Research Foundation, Southern Europe (Frontier Southern Europe), Rising Tide Foundation for Clinical Cancer Research (CCR-15–120; CCR-20–200; CCR-24–150), Pink Ribbon Switzerland, Swiss Cancer League (KLS-3361–02), San Salvatore Foundation, Swiss Group for Clinical Cancer Research, Clinical Cancer Research Foundation of Eastern Switzerland, Ms. Elisabetta Pavesi, Roche Diagnostics International, Verein Bärgüf, Swiss Cancer Foundation, Ms. Christine Hafner and Mr. Marc Wyss, Piajoh Fondazione di Famiglia, Gruppo Giovani Pazienti “Anna dai Capelli Corti”, and Schweizer Frauenlauf Bern — all in Switzerland; BIG Against Breast Cancer and the Baillet Latour Fund, Nationale loterij/Loterie nationale —all in Belgium; Breast Cancer Research Foundation (BCRF 24–011) and Gateway for Cancer Research (G-15–1900) and — both in the United States; Fondazione Umberto Veronesi, Italy; C & A, Germany; Dutch Cancer Society, the Netherlands (KaWeFis Batch7/7723); Norwegian Breast Cancer Society and Pink Ribbon — both in Norway; ELGC K.K. and Pink Ring — both in Japan; Mr. Yong Seop Lee, Ms. Sun Hee Kang, and Korean Breast Cancer Foundation — all in South Korea; and other private donors.

In North America, the Alliance for Clinical Trials in Oncology receives support from the National Cancer Institute of the National Institutes of Health (NIH) (Alliance for Clinical Trials in Oncology National Cancer Institute Community Oncology Research Program [NCORP] grant UG1CA189823) and the biorepository resource grant U24CA196171; the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network (ECOG-ACRIN) receives support under grant UG1CA189828; SWOG Cancer Research Network receives support under NIH grants UG1CA189974 and U10CA180888; and NRG Oncology receives support under NIH grant U10CA180868 and NCORP grant UG1CA189867. Canadian Cancer Trials Group (CCTG) participation in the trial is supported through its grant from the National Cancer Institute of the NIH (CA180863). Additional programmatic funding support for the CCTG is provided by the Canadian Cancer Society (707213) and the Canada Foundation for Innovation. In addition, the trial receives support from RETHINK Breast Cancer, Canada, the Susan G. Komen, United States and the Gilson Family Foundation, United States.

Footnotes

Disclosure

H.A.A. reports having a consultancy role for: Servier, PEP-Therapy, Linkinvax, Traverse Biotech, Nanoligent, Ferring Pharmaceuticals, and Guardant Health; receiving honorarium from Roche and Lilly; and having a speaker’s bureau role for AstraZeneca and NewBridge. M.C. reports serving as Scientific Committee Co-Chair for the International Breast Cancer Study Group. J.R.K. reports receiving unrestricted research grant funding from AstraZeneca, Novartis and Philips. E.W. reports receiving honoraria from Ferring Pharmaceuticals. H.C.F.M. reports receiving research grant funding (to institution) from: AstraZeneca, Roche, Daiichi-Sankyo, Pfizer, Sermonix, and Seagen. S. Borstnar reports receiving honoraria for speaker, consultancy/advisory from: AstraZeneca, Lilly, Pfizer, Novartis, Roche, MSD Oncology, Gilead, and Lek Sandoz. F.C. reports having a consultancy role for: Amgen, Astellas/Medivation, AstraZeneca, Bayer, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, Gilead, GlaxoSmithKline, Iqvia, Macrogenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, prIME Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva, and Touchime. S. E-A. reports receiving research grant funding (to institution) from: AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, Roche, Genentech, and Sanofi. G.V. reports receiving research grant funding from: Roche/Genentech, Ventana Medical Systems, and Dako/Agilent Technologies and receiving honoraria/consultation fees from: Dako/Agilent, Roche, MSD Oncology, AstraZeneca, Daiichi Sankyo, Pfizer, Eli Lilly, and Gilead. R.D.G. reports receiving research grant funding (to institution) from AstraZeneca, Merck and Roche. A.H.P. reports receiving royalties from UpToDate and serving as Chief Scientific Advisor for Susan G. Komen. All other authors have declared no conflicts of interest. All other authors have declared no conflicts of interest.

Registration

The trial was registered at ClinicalTrials.gov, NCT02308085.

Data sharing statement

After publication, access to deidentified participant data may be requested by researchers by submitting a proposal (to stat_center@ibcsg.org), which will be reviewed for scientific merit and feasibility in accordance with the Guidelines for Collaborative research (https://www.ibcsg.org/images/Member/Publi/Documents/Guidelines_for_Collaborative_Research_for_ETOP_IBCSG_Partners_Foundation_Dec_2022.pdf ) and data sharing policy (https://www.ibcsg.org/images/Member/Publi/Documents/Data_Sharing_Policy_for_IBCSG_Trials_Dec_2022.pdf) for IBCSG trials.

References

  • 1.American Cancer Society. Breast Cancer Facts and Figures 2024–2025. Atlanta: American Cancer Society, Inc. 2024. [Google Scholar]
  • 2.Ugai T, Sasamoto N, Lee HY et al. Is early-onset cancer an emerging global epidemic? Current evidence and future implications. Nat Rev Clin Oncol 2022; 19 (10): 656–673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Rosenberg SM, Newman LA, Partridge AH. Breast Cancer in Young Women: Rare Disease or Public Health Problem? JAMA Oncol 2015; 1 (7): 877–878. [DOI] [PubMed] [Google Scholar]
  • 4.Paluch-Shimon S, Cardoso F, Partridge AH et al. ESO-ESMO fifth international consensus guidelines for breast cancer in young women (BCY5). Ann Oncol 2022; 33 (11): 1097–1118. [DOI] [PubMed] [Google Scholar]
  • 5.Ruddy KJ, Gelber SI, Tamimi RM et al. Prospective study of fertility concerns and preservation strategies in young women with breast cancer. J Clin Oncol 2014; 32 (11): 1151–1156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Lambertini M, Di Maio M, Pagani O et al. The BCY3/BCC 2017 survey on physicians' knowledge, attitudes and practice towards fertility and pregnancy-related issues in young breast cancer patients. Breast 2018; 42: 41–49. [DOI] [PubMed] [Google Scholar]
  • 7.Lambertini M, Blondeaux E, Bruzzone M et al. Pregnancy After Breast Cancer: A Systematic Review and Meta-Analysis. J Clin Oncol 2021; 39 (29): 3293–3305. [DOI] [PubMed] [Google Scholar]
  • 8.Lambertini M, Blondeaux E, Agostinetto E et al. Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study. JAMA 2023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Gerstl B, Sullivan E, Ives A et al. Pregnancy Outcomes After a Breast Cancer Diagnosis: A Systematic Review and Meta-analysis. Clin Breast Cancer 2018; 18 (1): e79–e88. [DOI] [PubMed] [Google Scholar]
  • 10.Abel MK, Wald K, Sinha N et al. Conception after chemotherapy: post-chemotherapy method of conception and pregnancy outcomes in breast cancer patients. J Assist Reprod Genet 2021; 38 (7): 1755–1765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Pan H, Gray R, Braybrooke J et al. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. N Engl J Med 2017; 377 (19): 1836–1846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Pagani O, Partridge A, Korde L et al. Pregnancy after breast cancer: if you wish, ma'am. Breast Cancer Res Treat 2011; 129 (2): 309–317. [DOI] [PubMed] [Google Scholar]
  • 13.Partridge AH, Niman SM, Ruggeri M et al. Who are the women who enrolled in the POSITIVE trial: A global study to support young hormone receptor positive breast cancer survivors desiring pregnancy. Breast 2021; 59: 327–338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Partridge AH, Niman SM, Ruggeri M et al. Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer. N Engl J Med 2023; 388 (18): 1645–1656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Azim HA Jr., Niman SM, Partridge AH et al. Fertility Preservation and Assisted Reproduction in Patients With Breast Cancer Interrupting Adjuvant Endocrine Therapy to Attempt Pregnancy. J Clin Oncol 2024; 42 (23): 2822–2832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Hudis CA, Barlow WE, Costantino JP et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol 2007; 25 (15): 2127–2132. [DOI] [PubMed] [Google Scholar]
  • 17.Francis PA, Pagani O, Fleming GF et al. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. N Engl J Med 2018; 379 (2): 122–137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Sun Z, Niman SM, Pagani O et al. Estimation of historical control rate for a single arm de-escalation study - Application to the POSITIVE trial. Breast 2020; 53: 1–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Agostinetto E, Curigliano G, Piccart M. Emerging treatments in HER2-positive advanced breast cancer: Keep raising the bar. Cell Rep Med 2024; 5 (6): 101575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Partridge AH, Ruddy KJ, Gelber S et al. Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer. Fertil Steril 2010; 94 (2): 638–644. [DOI] [PubMed] [Google Scholar]
  • 21.Poorvu PD, Gelber SI, Zheng Y et al. Pregnancy after breast cancer: Results from a prospective cohort of young women with breast cancer. Cancer 2021; 127 (7): 1021–1028. [DOI] [PubMed] [Google Scholar]
  • 22.Anderson RA, Lambertini M, Hall PS et al. Survival after breast cancer in women with a subsequent live birth: Influence of age at diagnosis and interval to subsequent pregnancy. Eur J Cancer 2022; 173: 113–122. [DOI] [PubMed] [Google Scholar]
  • 23.Hamilton BE, Ventura SJ. Fertility and abortion rates in the United States, 1960–2002. Int J Androl 2006; 29 (1): 34–45. [DOI] [PubMed] [Google Scholar]
  • 24.Matthews TJ, Hamilton BE. Mean age of mothers is on the rise: United States 2000–2014. In: Services USDoHaH, ed.: Center for Disease Control and Prevention, National Center for Health Statistics Data Brief; 2014:1–8. [Google Scholar]
  • 25.DeSantis CE, Ma J, Gaudet MM et al. Breast cancer statistics, 2019. CA Cancer J Clin 2019; 69 (6): 438–451. [DOI] [PubMed] [Google Scholar]
  • 26.Lambe M, Hsieh C, Trichopoulos D et al. Transient increase in the risk of breast cancer after giving birth. N Engl J Med 1994; 331 (1): 5–9. [DOI] [PubMed] [Google Scholar]
  • 27.Surbone A, Petrek JA. Pregnancy after breast cancer. The relationship of pregnancy to breast cancer development and progression. Crit Rev Oncol Hematol 1998; 27 (3): 169–178. [DOI] [PubMed] [Google Scholar]
  • 28.Giordano SH. POSITIVE Results for Breast Cancer Survivors Who Desire Pregnancy. N Engl J Med 2023; 388 (18): 1709–1710. [DOI] [PubMed] [Google Scholar]
  • 29.Azim HA Jr, Kroman N, Paesmans M et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J Clin Oncol 2013; 31 (1): 73–79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Sankila R, Heinavaara S, Hakulinen T. Survival of breast cancer patients after subsequent term pregnancy: "healthy mother effect". Am J Obstet Gynecol 1994; 170 (3): 818–823. [DOI] [PubMed] [Google Scholar]
  • 31.Early Breast Cancer Trialists' Collaborative G. Tamoxifen for early breast cancer. Cochrane Database Syst Rev 2001. (1): CD000486. [DOI] [PubMed] [Google Scholar]
  • 32.Early Breast Cancer Trialists' Collaborative G. Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials. Lancet Oncol 2022; 23 (3): 382–392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Burstein HJ, Lacchetti C, Anderson H et al. Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression. J Clin Oncol 2016; 34 (14): 1689–1701. [DOI] [PubMed] [Google Scholar]
  • 34.Colleoni M, Luo W, Karlsson P et al. Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2018; 19 (1): 127–138. [DOI] [PubMed] [Google Scholar]
  • 35.Ribi K, Luo W, Colleoni M et al. Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial. Br J Cancer 2019; 120 (10): 959–967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Dumas E, Jochum F, Coussy F et al. Explaining the Relationships Between Age, Endocrine Therapy Persistence, and Risk of Recurrence in Hormone Receptor-Positive Early Breast Cancer: A Nationwide Cohort Study. J Clin Oncol 2025; 43 (16): 1863–1874. [DOI] [PubMed] [Google Scholar]
  • 37.Kepley JM, Bates K, Mohiuddin SS. Physiology, Maternal Changes. [Updated 2023 Mar 12]. In: StatPearls [Internet]. 2025. Treasure Island (FL): StatPearls Publishing; 2025. [PubMed] [Google Scholar]
  • 38.Virassamy B, Caramia F, Savas P et al. Parity and lactation induce T-cell-mediated breast cancer protection. Nature 2026; 649 (8096): 449–459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Wesselink AK, Rothman KJ, Hatch EE et al. Age and fecundability in a North American preconception cohort study. Am J Obstet Gynecol 2017; 217 (6): 667 e661–667 e668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Lobo RA. Potential options for preservation of fertility in women. N Engl J Med 2005; 353 (1): 64–73. [DOI] [PubMed] [Google Scholar]
  • 41.Waks AG, Partridge AH. Fertility Preservation in Patients With Breast Cancer: Necessity, Methods, and Safety. J Natl Compr Canc Netw 2016; 14 (3): 355–363. [DOI] [PubMed] [Google Scholar]
  • 42.Lambertini M, Peccatori FA, Demeestere I et al. Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines(dagger). Ann Oncol 2020; 31 (12): 1664–1678. [DOI] [PubMed] [Google Scholar]
  • 43.Su HI, Lacchetti C, Letourneau J et al. Fertility Preservation in People With Cancer: ASCO Guideline Update. J Clin Oncol 2025; 43 (12): 1488–1515. [DOI] [PubMed] [Google Scholar]
  • 44.The American College of Obstetricians and Gynecologists Committee on Gynecologic Practice; The Practice Committee of the American Society for Reproductive Medicine. Committee Opinion: Female Age-Related Fertility Decline. Number 589. 2020. [Google Scholar]
  • 45.World Population Review. https://worldpopulationreview.com/country-rankings/total-fertility-rate. 2025. [Google Scholar]
  • 46.Bignami S, Endrich M, Natale F et al. Low Fertility in the EU: A Review of Trends and Drivers. In: Commission E, ed. JRC137492. Ispra; 2024. [Google Scholar]
  • 47.Langagergaard V, Gislum M, Skriver MV et al. Birth outcome in women with breast cancer. Br J Cancer 2006; 94 (1): 142–146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Dalberg K, Eriksson J, Holmberg L. Birth outcome in women with previously treated breast cancer--a population-based cohort study from Sweden. PLoS Med 2006; 3 (9): e336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Hartnett KP, Mertens AC, Kramer MR et al. Pregnancy after cancer: Does timing of conception affect infant health? Cancer 2018; 124 (22): 4401–4407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Buonomo B, Brunello A, Noli S et al. Tamoxifen Exposure during Pregnancy: A Systematic Review and Three More Cases. Breast Care (Basel) 2020; 15 (2): 148–156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Braems G, Denys H, De Wever O et al. Use of tamoxifen before and during pregnancy. Oncologist 2011; 16 (11): 1547–1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Saha P, Regan MM, Pagani O et al. Treatment Efficacy, Adherence, and Quality of Life Among Women Younger Than 35 Years in the International Breast Cancer Study Group TEXT and SOFT Adjuvant Endocrine Therapy Trials. J Clin Oncol 2017; 35 (27): 3113–3122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Partridge AH, Wang PS, Winer EP et al. Nonadherence to adjuvant tamoxifen therapy in women with primary breast cancer. J Clin Oncol 2003; 21 (4): 602–606. [DOI] [PubMed] [Google Scholar]
  • 54.Hershman DL, Kushi LH, Shao T et al. Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol 2010; 28 (27): 4120–4128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Huiart L, Bouhnik AD, Rey D et al. Early discontinuation of tamoxifen intake in younger women with breast cancer: is it time to rethink the way it is prescribed? Eur J Cancer 2012; 48 (13): 1939–1946. [DOI] [PubMed] [Google Scholar]
  • 56.Ransohoff JD, Lewinsohn RM, Dickerson J et al. Endocrine Therapy Interruption, Resumption, and Outcomes Associated With Pregnancy After Breast Cancer. JAMA Oncol 2025; 11 (4): 423–426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Francis PA, Fleming GF, Lang I et al. Adjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results From SOFT. J Clin Oncol 2023; 41 (7): 1370–1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Pagani O, Walley BA, Fleming GF et al. Adjuvant Exemestane With Ovarian Suppression in Premenopausal Breast Cancer: Long-Term Follow-Up of the Combined TEXT and SOFT Trials. J Clin Oncol 2023; 41 (7): 1376–1382. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Author accepted suppl file
NIHMS2198591-supplement-Author_accepted_suppl_file.docx (661.8KB, docx)

Data Availability Statement

After publication, access to deidentified participant data may be requested by researchers by submitting a proposal (to stat_center@ibcsg.org), which will be reviewed for scientific merit and feasibility in accordance with the Guidelines for Collaborative research (https://www.ibcsg.org/images/Member/Publi/Documents/Guidelines_for_Collaborative_Research_for_ETOP_IBCSG_Partners_Foundation_Dec_2022.pdf ) and data sharing policy (https://www.ibcsg.org/images/Member/Publi/Documents/Data_Sharing_Policy_for_IBCSG_Trials_Dec_2022.pdf) for IBCSG trials.

RESOURCES