Understanding Incomplete Ovarian Function Suppression in Premenopausal Breast Cancer Patients on Anti-Hormone Therapy

Table of Contents

• Key Points
• Why This Research Matters
• What This Study Set Out to Do
• How the Study Was Conducted (Study Methods)
• The E2 Monitoring Protocol
• Who Was Included in the Study
• Key Findings: How Many Patients Achieved Complete OFS
• Patient Characteristics: Complete vs. Incomplete OFS
• What Happened When GnRH Agonists Were Changed
• Detailed E2 Level Analysis
• How These Findings Compare to Previous Research
• What This Means for Patients
• Study Limitations
• Recommendations for Patients
• Frequently Asked Questions
• Source Information

Key Points

• In a study of 85 premenopausal women with hormone receptor-positive breast cancer, 17 (20%) had incomplete ovarian function suppression on a GnRH agonist plus anti-hormone therapy.
• In that study, complete suppression meant estradiol at or below 2.72 pg/mL on an aromatase inhibitor, or at or below 21 pg/mL on tamoxifen, for three consecutive draws.
• Of 14 patients who changed their GnRH agonist, 7 (50%) achieved complete ovarian function suppression; 5 continued to have incomplete suppression.
• Among those 14 patients, all 7 with prior chemotherapy achieved complete suppression versus 1 of 5 who never had chemotherapy (p = 0.010).
• The study was retrospective, at one health system, with a small sample; no universally accepted estradiol cutoff defines complete ovarian function suppression.

Why This Research Matters

Breast cancer is the most common cancer among women worldwide. Approximately 70% of newly diagnosed breast cancer cases are hormone receptor-positive (HR+), meaning that estrogen and other hormones fuel the cancer's growth. These hormones promote breast cell proliferation, and estrogen metabolites may even initiate DNA damage and mutations. This is why anti-hormone therapy (also called endocrine therapy) is a cornerstone of breast cancer treatment.

For premenopausal women with HR+ breast cancer, suppressing ovarian function has become a critical part of treatment. The ovaries are the primary source of estrogen in premenopausal women, so turning off ovarian function—through medication, surgery, or radiation—can starve hormone-sensitive tumors of the estrogen they need to grow.

Two landmark studies, the Tamoxifen and Exemestane Trial (TEXT) and the Suppression of Ovarian Function Trial (SOFT), were initiated in 2003 by the International Breast Cancer Study Group. These randomized Phase 3 trials involved premenopausal women with HR+ early breast cancer and were designed to measure the impact of ovarian function suppression when combined with adjuvant tamoxifen or the aromatase inhibitor (AI) exemestane.

In both trials, OFS was achieved using triptorelin 3.75 mg given intramuscularly every 28 days, bilateral surgical removal of the ovaries (oophorectomy), or ovarian irradiation—with approximately 95% of patients using the GnRH agonist triptorelin. The results were striking. At 8 years, the disease-free survival (DFS) rates were:

• 78.9% with tamoxifen alone
• 83.2% with tamoxifen plus OFS
• 85.9% with aromatase inhibitor plus OFS

These findings highlighted the significant benefits of ovarian suppression and established OFS combined with tamoxifen or an AI as the standard of care for high-risk premenopausal women with HR+ breast cancer.

However, concerns soon emerged about whether some patients were achieving truly complete ovarian suppression. The SOFT Estrogen Substudy (SOFT-EST) prospectively evaluated estradiol (E2) levels in patients receiving exemestane plus triptorelin. While 66% of patients showed a persistent reduction in E2 levels during the first 12 months, at least 17% of patients had an E2 level greater than 2.72 pg/mL at each time point—a finding classified as ovarian escape (OE), or incomplete OFS.

Similarly, research by Burns and colleagues found that about a quarter of premenopausal women do not attain adequate OFS within the first three months of GnRH agonist therapy based on E2 levels. Age was a significant risk factor: younger women were more likely to experience ovarian escape. While body mass index (BMI), prior chemotherapy, and the specific drug used (tamoxifen versus AI) did not correlate with ovarian escape in Burns' study, the SOFT-EST study did find increased rates of incomplete OFS in patients with higher BMI and in those who had not received prior chemotherapy.

In premenopausal patients receiving a GnRH agonist combined with an AI, suboptimal E2 suppression is especially concerning. The reduced estrogen levels caused by the AI can actually activate the hypothalamic-pituitary-ovarian axis, potentially stimulating the ovaries to produce more estrogen.

What This Study Set Out to Do

Major oncology organizations have weighed in on this issue. The National Comprehensive Cancer Network (NCCN) states that serial assessments of circulating estradiol are "mandatory" in premenopausal patients being considered for adjuvant endocrine therapy with an AI, "to assure a true postmenopausal state." The American Society of Clinical Oncology (ASCO) similarly advises that "clinicians should be alert to the possibility of incomplete ovarian suppression with GnRH agonist therapy and should evaluate patients in whom there is concern for residual ovarian function."

However, neither organization provides specific laboratory cutoff values to determine whether residual ovarian function is present. Notably, NCCN does acknowledge that "clear criteria to guide interpretation of FSH and estradiol in this population is lacking."

At Froedtert & the Medical College of Wisconsin (MCW), no standardized protocol existed for monitoring OFS at the time this study was designed. The institution's preferred formulary GnRH agonist was leuprolide acetate (Eligard) 7.5 mg subcutaneous (SQ) every month or 22.5 mg SQ every 3 months—a medication that was not included in the SOFT/TEXT trials and is not as widely studied in breast cancer patients. Leuprolide was chosen as the preferred agent because it offers a more comfortable injection and is more cost-effective for patients.

The authors of this study hypothesized that incomplete OFS rates at their institution might actually be lower than those reported in SOFT-EST, because the leuprolide dose used (7.5 mg) is higher than the triptorelin dose (3.75 mg) studied in the landmark trials. The primary aim was to develop and implement a protocol for monitoring E2 levels based on NCCN and ASCO recommendations, then retrospectively analyze the results.

How the Study Was Conducted (Study Methods)

This was a single-health system, retrospective study conducted at Froedtert & MCW. Researchers reviewed electronic health records of female patients with HR+ breast cancer who were receiving a GnRH agonist combined with either tamoxifen or an AI between October 1, 2022, and May 1, 2024—an evaluation period of approximately 18 months. The study was approved by the Institutional Review Board of the health system; because of the retrospective design, individual consent to participate was not required.

The ambulatory oncology pharmacist was responsible for ordering and monitoring E2 levels according to the institution's new monitoring protocol. This protocol was developed by the project team and reviewed and approved by the health system's Pharmacy & Therapeutics Committee.

The E2 Monitoring Protocol

The protocol worked as follows:

1. A baseline E2 and follicle stimulating hormone (FSH) level was drawn on all new GnRH agonist patients.
2. Tamoxifen therapy was initiated at the time of the GnRH agonist injection or approximately 28 days afterward.
3. Aromatase inhibitors were initiated at least 28 days after the start of the GnRH agonist.
4. After 28 days on concurrent therapy (GnRH agonist plus tamoxifen or AI), subsequent E2/FSH levels were drawn approximately 28 days apart for patients on monthly injections, and approximately 84 days apart for patients on every-3-month injections.
5. If the E2 level was ≤ 2.72 pg/mL for those on AI therapy, or ≤ 21 pg/mL for those on tamoxifen therapy, for three consecutive draws, the pharmacist notified the primary oncologist that the definition of OFS had been met, and no further E2 monitoring was required.
6. If the E2 level was above these thresholds, the provider was notified of the elevated level. After the second consecutive high level, the pharmacist notified the oncologist that the patient met the definition of incomplete OFS, and the oncologist could consider changing the GnRH agonist dose, frequency, or formulation as clinically indicated.

All E2 levels were analyzed by ARUP Laboratories in Salt Lake City, Utah, which uses a testing method with increased sensitivity capable of measuring levels down to just 2 pg/mL. This high sensitivity was critical for accurately detecting whether ovarian suppression was truly complete.

Who Was Included in the Study

Patients were eligible for inclusion if they met all of the following criteria:

• Greater than 18 years old
• Female
• Deemed premenopausal by their treating oncologist
• Diagnosed with HR+ breast cancer
• Receiving a GnRH agonist with tamoxifen or an AI
• Planned to continue treatment for a minimum of three months

Patients were excluded if they were younger than 18 years old, were assigned male sex at birth, or were female patients receiving concurrent chemotherapy with a GnRH agonist for fertility preservation (rather than cancer treatment).

The primary outcome was the proportion of patients failing to achieve OFS for three consecutive levels per the E2 monitoring protocol. Secondary outcomes included the number of provider interventions initiated for patients failing to achieve OFS, and the proportion of patients failing to achieve OFS stratified by age, BMI, GnRH agonist received, and prior receipt of chemotherapy.

Statistical analysis used chi-squared or Fisher's exact tests for nominal (categorical) data, and the Mann Whitney U or Student's t-test for continuous data. Analysis was completed using Microsoft Excel and SPSS Statistics version 29.0.

Key Findings: How Many Patients Achieved Complete OFS

A total of 85 patients were reviewed at the time of analysis. The results broke down as follows:

• 53 patients (62.4%) achieved complete OFS, defined as three consecutive E2 levels within the target range
• 17 patients (20%) demonstrated incomplete OFS, defined as two consecutive E2 levels above goal
• 7 patients (8.2%) had not yet had enough consecutive levels to determine whether they had complete or incomplete OFS, so E2 lab monitoring continues for them
• 8 patients (9.4%) declined lab monitoring altogether

Reasons why the 7 patients in the "monitoring continues" group had not met either definition included missed lab draws, isolated E2 elevations, late injections that voided levels per provider preference, and newly enrolled patients who simply had not had enough levels drawn by the time of the analysis cutoff.

The average age of all patients was 41.2 years (range 26–55), and the average body mass index was 28.5 kg/m² (range 17.4–49.9).

In terms of treatment history, 57 patients (67.1%) had received chemotherapy for their breast cancer, while 28 patients (32.9%) had not received any chemotherapy prior to starting a GnRH agonist. Of those who had chemotherapy, 30 patients (35.3%) received it as neoadjuvant treatment (before surgery), and 27 patients (31.8%) received it as adjuvant treatment (after surgery).

Breast cancer stages among participants were:

• Stage I: 41 patients (48.2%)
• Stage II: 23 patients (27.1%)
• Stage III: 11 patients (12.9%)
• Stage IV: 10 patients (11.8%)

The GnRH agonist agents used were primarily leuprolide in various formulations:

• Leuprolide 7.5 mg SQ monthly: 69 patients (81.2%)
• Leuprolide 22.5 mg SQ every 3 months: 5 patients (5.9%)
• Leuprolide 3.75 mg IM monthly: 4 patients (4.7%)
• Leuprolide 11.25 mg IM every 3 months: 1 patient (1.2%)
• Goserelin 3.6 mg SQ monthly: 5 patients (5.9%)
• Goserelin 10.8 mg SQ every 3 months: 1 patient (1.2%)

For concurrent anti-hormone therapy, 78 patients (91.7%) were on an aromatase inhibitor and 7 patients (8.3%) were on tamoxifen. The specific agents were anastrozole (57.6%), letrozole (18.8%), exemestane (15.3%), and tamoxifen (8.3%).

Patient Characteristics: Complete vs. Incomplete OFS

Researchers compared the characteristics of patients who achieved complete OFS against those who had incomplete OFS. The two groups were largely similar in most respects:

• Age: 42.77 years (complete) vs. 41.8 years (incomplete), p = 0.390—not statistically significant
• BMI: 29.44 kg/m² (complete) vs. 29.1 kg/m² (incomplete), p = 0.462—not statistically significant
• Prior chemotherapy: 66% of the complete group had received chemotherapy vs. 58.8% of the incomplete group, p = 0.762—not statistically significant

Both groups consisted largely of patients with Stage I disease (45.3% of the complete OFS group vs. 58.8% of the incomplete OFS group). Interestingly, the complete OFS group had more patients with Stage IV disease (18.9%) compared to the incomplete OFS group (0%). The majority of patients in both groups received leuprolide 7.5 mg monthly SQ injections and were on aromatase inhibitors. Only five patients with complete OFS and one patient with incomplete OFS were on tamoxifen.

What Happened When GnRH Agonists Were Changed

Of the 17 patients who demonstrated incomplete OFS, 14 underwent a change in their GnRH agonist as an intervention aimed at achieving complete OFS. The specific changes were:

• 12 patients switched from leuprolide SQ monthly injections to goserelin SQ monthly injections
• 1 patient switched from goserelin SQ monthly injection to leuprolide SQ monthly injection
• 1 patient switched from leuprolide SQ monthly injections to leuprolide SQ every-3-month injections (to improve compliance)

Three patients had no change made based on provider preference. One of these three—who remained on leuprolide SQ every-3-month injections—did eventually achieve OFS with continued monitoring.

Among the 14 patients who had a change made to their GnRH therapy:

• 7 patients (50%) achieved complete OFS after the intervention
• 5 patients (35.7%) continued to have incomplete OFS despite the change
• 2 patients decided to discontinue future E2 lab monitoring

When comparing those who achieved OFS after switching versus those who continued to have incomplete OFS, one difference stood out as statistically significant: prior receipt of chemotherapy. Among patients who had received chemotherapy before, 100% achieved complete OFS after switching GnRH agonists, compared to only 20% of those who had never received chemotherapy (p = 0.010).

Other characteristics were not statistically significant between these two groups, though some numerical trends were noted:

• Patients with continued incomplete OFS were younger on average (40 years vs. 42 years)
• Patients with continued incomplete OFS had a higher average BMI (31.5 kg/m² vs. 27.3 kg/m²)

Detailed E2 Level Analysis

Researchers also looked more closely at the E2 levels in patients who continued to have incomplete OFS after a GnRH switch, as well as those whose monitoring was still pending. They evaluated two additional, less stringent E2 cutoff points to better understand the degree of ovarian suppression being achieved.

For the 5 patients with continued incomplete OFS (48 total E2 levels drawn):

• 27% of isolated E2 levels were ≤ 2.72 pg/mL (the strict definition used for complete OFS on AI therapy)
• 56.3% of isolated E2 levels were ≤ 5 pg/mL
• 85.4% of isolated E2 levels were ≤ 10 pg/mL

For the 7 patients with labs still pending (24 total E2 levels drawn):

• 16.7% of isolated E2 levels were ≤ 2.72 pg/mL
• 70.8% of isolated E2 levels were ≤ 5 pg/mL
• 79.2% of isolated E2 levels were ≤ 10 pg/mL

These findings suggest that even among patients classified as having incomplete OFS under the strict 2.72 pg/mL cutoff, the majority were achieving E2 levels well below 10 pg/mL—levels that might still be considered close to the postmenopausal range. This raises important questions about whether the current strict cutoff is clinically meaningful for all patients.

How These Findings Compare to Previous Research

In this single-health system evaluation, 17 patients (20%) demonstrated incomplete OFS over the 18-month period—a rate very similar to the 17% reported in the SOFT-EST substudy. This consistency is notable because Froedtert & MCW used leuprolide acetate (Eligard) 7.5 mg SQ monthly as its preferred agent, whereas SOFT-EST used triptorelin 3.75 mg IM every 28 days.

Previous studies have associated younger age, higher BMI, and being chemotherapy-naïve with a higher incidence of incomplete OFS. This study's findings were consistent in some ways:

• Age: The average age was similar between complete and incomplete OFS groups (42.77 vs. 41.8 years), but the age range was lower for those with incomplete OFS (28–45 years) compared to complete OFS (26–55 years).
• BMI: The average BMI was numerically higher in the incomplete OFS group, with a broader range (17.4–49.9) compared to the complete OFS group (20.2–43.1).
• Chemotherapy history: Chemotherapy-naïve patients had a higher incidence of incomplete OFS—41.2% of the incomplete OFS group had no prior chemotherapy compared to 34.5% of the complete OFS group. More dramatically, among patients who switched GnRH agonists, 100% of those with prior chemotherapy achieved complete OFS versus only 20% of chemotherapy-naïve patients (p = 0.010).

These results align with the SOFT-EST findings, which also reported increased incomplete OFS in patients with higher BMI and in those who were chemotherapy-naïve. The mechanism behind this is not entirely clear, but it may relate to how chemotherapy affects ovarian reserve and function, or to differences in how the body metabolizes or responds to GnRH agonists.

It is important to note that medical literature lacks a universally agreed-upon E2 level that defines true menopause or complete OFS. This lack of clarity has created significant variability in the management of anti-hormone therapy across different health systems. A recent survey conducted through the ASCO Research Survey Pool revealed both consistencies and inconsistencies with the monitoring practices at Froedtert & MCW, highlighting that standardized methods for evaluating incomplete OFS are not consistently implemented across different institutions.

What This Means for Patients

For premenopausal women with HR+ breast cancer, this study offers several important takeaways:

First, incomplete ovarian suppression is a real and relatively common problem, affecting roughly 1 in 5 patients. If a patient's ovaries continue producing estrogen despite GnRH agonist therapy, the anti-hormone treatment may not be working as effectively as it should—particularly when combined with an aromatase inhibitor, which relies on the ovaries being fully suppressed to achieve its effect.

Second, monitoring matters. The simple act of checking E2 levels monthly or every three months revealed that 20% of patients were not achieving complete OFS. Without monitoring, this would have gone unnoticed. NCCN guidelines mandate this monitoring, and ASCO recommends vigilance.

Third, a change in medication can help. Half of the patients who switched GnRH agonists successfully achieved complete OFS. This means that if a patient is found to have incomplete suppression, switching from one GnRH agonist (e.g., leuprolide) to another (e.g., goserelin) or changing the dose or frequency can be an effective solution—though not for everyone.

Fourth, patients who never received chemotherapy may need extra attention. The strong statistical finding (p = 0.010) that chemotherapy-naïve patients were more likely to continue having incomplete OFS even after switching medications suggests that these patients may have more resilient ovarian function. This could be because chemotherapy damages ovarian tissue, making residual estrogen production less likely, whereas patients who never had chemotherapy retain fuller ovarian function that is more difficult to suppress.

Study Limitations

This study has several limitations that should be considered when interpreting the results:

• Retrospective design: Because the analysis was conducted retrospectively using electronic health records, it carries the inherent limitations of observational data, including potential documentation gaps and inability to control for all confounding factors.
• Single health system: The findings come from one institution (Froedtert & MCW) and may not be generalizable to other settings with different patient populations or treatment protocols.
• Small sample size: With only 85 patients total, and just 17 with incomplete OFS, the statistical power is limited. The subgroup analysis of patients who switched GnRH agonists involved only 12 patients (7 with OFS after intervention, 5 with continued incomplete OFS), making the p = 0.010 finding notable but in need of validation in larger studies.
• No standardized E2 cutoff: The study used the SOFT-EST threshold of 2.72 pg/mL for patients on AIs, but as the authors acknowledge, there is no universally accepted definition of complete OFS. The finding that many "incomplete" patients actually had E2 levels well below 10 pg/mL raises questions about whether the strict threshold is clinically meaningful for all patients.
• Discrepancy in primary outcome definition: The abstract describes the primary outcome as failing to achieve OFS for "two consecutive levels," while the endpoints section and results describe "three consecutive levels." This inconsistency reflects the real-world complexity of defining OFS, and readers should interpret the published results carefully.
• Patient preference and adherence: Eight patients (9.4%) declined lab monitoring entirely, and two patients with incomplete OFS chose to discontinue monitoring after their GnRH agonist was changed. These patients could not be assessed, potentially affecting the reported rates.
• Short follow-up: The 18-month evaluation period may not capture longer-term patterns of ovarian escape or late recovery of ovarian function.

Recommendations for Patients

Based on this study and current clinical guidelines, patients and their care teams may want to consider the following:

1. Ask about E2 monitoring. If you are a premenopausal woman receiving a GnRH agonist (such as leuprolide, goserelin, or triptorelin) combined with an aromatase inhibitor, ask your oncologist whether your estradiol levels are being checked regularly. Current NCCN guidelines consider this monitoring "mandatory."
2. Understand your target levels. While there is debate about the exact cutoff, this study defined complete OFS as E2 ≤ 2.72 pg/mL for patients on aromatase inhibitors and ≤ 21 pg/mL for patients on tamoxifen. Monitoring should occur after at least 28 days on concurrent therapy and then at regular intervals aligned with your injection schedule.
3. Know if you are at higher risk. If you are younger, have a higher BMI, or never received chemotherapy, you may be at increased risk for incomplete ovarian suppression. This does not mean your treatment is failing—it simply means that closer monitoring may be warranted.
4. Consider a medication change if incomplete OFS is confirmed. This study found that switching GnRH agonists (for example, from leuprolide to goserelin) helped half of patients achieve complete OFS. If two consecutive E2 levels are above goal, talk to your doctor about whether changing the dose, frequency, or formulation of your GnRH agonist makes sense.
5. Stay consistent with your injections. Late or missed injections can cause temporary rises in estrogen levels and may complicate the interpretation of E2 monitoring results. Timing matters.
6. Keep monitoring even if levels look good. Once three consecutive E2 levels are within goal, this study's protocol allowed monitoring to stop. But if you or your doctor have ongoing concerns about residual ovarian function, periodic rechecking may still be reasonable.

Ultimately, this study reinforces an important message: ovarian suppression is not always complete, and a simple blood test can help ensure that anti-hormone therapy is working as effectively as possible. For patients who are not achieving full suppression, a change in medication may offer a path toward better treatment outcomes.

Frequently Asked Questions

What is incomplete ovarian function suppression?

In premenopausal women with hormone receptor-positive breast cancer, ovarian function suppression is meant to stop the ovaries making estrogen. Incomplete suppression means estrogen levels stay above the target despite treatment with a GnRH agonist plus anti-hormone therapy. In a study of 85 women, 17 (20%) had two consecutive estradiol levels above goal, which was called incomplete ovarian function suppression.

How common is incomplete ovarian suppression on GnRH agonist therapy?

In a study of 85 premenopausal women with hormone receptor-positive breast cancer receiving a GnRH agonist plus anti-hormone therapy, 17 patients (20%) had incomplete ovarian function suppression, defined as two consecutive estradiol levels above goal. This rate was similar to the 17% reported in the SOFT-EST substudy, even though the GnRH agonist used differed between the two.

If my estradiol level is high, what happens next?

In the protocol, the pharmacist notified the oncologist after the second consecutive high estradiol level, and the oncologist could consider changing the GnRH agonist dose, frequency, or formulation. Of 17 patients with incomplete suppression, 14 changed their GnRH agonist; 7 of those 14 (50%) then achieved complete ovarian function suppression, while 5 continued to have incomplete suppression.

Who was more likely to keep having incomplete suppression after switching drugs?

Among the 14 patients who changed their GnRH agonist, all 7 who had received chemotherapy before achieved complete ovarian function suppression, compared with only 1 of 5 patients who had never received chemotherapy (p = 0.010). This suggests chemotherapy-naïve patients may have more resilient ovarian function, though the subgroup was small and the finding needs validation in larger studies.

Do I need estradiol monitoring if I am premenopausal and on an aromatase inhibitor?

The National Comprehensive Cancer Network states that serial estradiol assessments are mandatory in premenopausal patients being considered for adjuvant endocrine therapy with an aromatase inhibitor, to confirm a true postmenopausal state. The American Society of Clinical Oncology advises clinicians to be alert to possible incomplete ovarian suppression with GnRH agonist therapy and to evaluate patients when there is concern about residual ovarian function.

What are the limitations of the evidence on incomplete ovarian suppression?

The findings come from a retrospective review of 85 patients at a single health system, with only 17 cases of incomplete suppression and 12 patients in the drug-switch analysis, so statistical power is limited. There is no universally accepted estradiol cutoff defining complete ovarian function suppression, and 8 patients (9.4%) declined monitoring, which may affect the reported rates.

If my estradiol level stays above 2.72 pg/mL on a GnRH agonist plus an aromatase inhibitor, when should I seek a second opinion?

Incomplete ovarian function suppression affects roughly 1 in 5 premenopausal women on a GnRH agonist with anti-hormone therapy. If two consecutive estradiol levels are above goal, a change in the GnRH agonist dose, frequency, or formulation may help; switching agents helped half of patients achieve complete suppression. Patients who never received chemotherapy were more likely to remain unsuppressed after a switch. A second opinion can review your estradiol monitoring and whether your suppression is truly complete. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Evaluation and management of incomplete ovarian function suppression in premenopausal breast cancer patients receiving anti-hormone therapy

Authors: Ruchi Patel, Elizabeth Weil, Sara Bugamelli, Emma Carroll, Kylie Steinke, Erinn Stockhausen, John Burfeind, Colin Mooney, Janet Retseck, Deepika Sriram, Jutta Deininger, Angela Halbach, Maressa Sweeney, Sailaja Kamaraju, Lubna N. Chaudhary, and Yee Chung Cheng

Journal: Breast Cancer Research (2025) 27:147

DOI: https://doi.org/10.1186/s13058-025-01979-x

Key references cited in the original article include: Pagani et al., N Engl J Med 371(2):107–118, 2014 (SOFT/TEXT trials); Bellet et al., J Clin Oncol 34(14):1584–1593, 2016 (SOFT-EST substudy); Burstein et al., J Clin Oncol 37(5):423–438, 2019 (ASCO guidelines); and NCCN Clinical Practice Guidelines in Oncology: Breast Cancer, Version 2.2024.

This patient-friendly article is based on peer-reviewed research. It was written to help patients understand the study's findings but should not replace individualized medical advice from your oncology care team.