Fertility Decisions Influenced by Age and Parental Status in Premenopausal Breast Cancer

Most premenopausal women with early breast cancer accepted gonadotropin-releasing hormone agonist (GnRHa) therapy during chemotherapy to preserve ovarian function, whereas uptake of cryopreservation strategies remained lower, particularly in older premenopausal patients, according to data from the Premenopausal Breast Cancer Patients’ Fertility Preservation (PREFER) study, a large Italian multicenter prospective cohort.

The prospective cohort evaluated fertility preservation strategies in this patient population, and data were shared at the 2025 San Antonio Breast Cancer Symposium. Among patients aged 41 to 45 years, 75% received GnRHa alone, and 25% declined any procedure. Among patients 40 years or younger, 89% received GnRHa, 25% underwent cryopreservation, and 9% underwent no procedure. Acceptance varied according to hormone receptor status, with higher GnRHa uptake in patients with hormone receptor-positive disease. Factors associated with cryopreservation acceptance included younger age, absence of prior children, more recent year of diagnosis, and lower tumor grade.

“Most premenopausal women with early breast cancer accepted the use of a genetic agonist during chemotherapy to preserve ovarian function. Factors associated with acceptance included younger age at diagnosis, no prior children, more recent year of diagnosis, and lower tumor grade,” explained Matteo Lambertini, associate professor and consultant in medical oncology at the University of Genova and IRCCS Policlinico San Martino Hospital in Genova, Italy.

Importantly, controlled ovarian stimulation for oocyte cryopreservation did not negatively impact disease-free survival or overall survival.

PREFER Study: A National Oncofertility Initiative

Oncofertility counseling is recommended for all premenopausal women with newly diagnosed early breast cancer who are candidates for chemotherapy. Standard approaches include cryopreservation of oocytes, embryos, and ovarian tissue, with concurrent GnRHa therapy recommended during chemotherapy to preserve ovarian function. However, data on the uptake of these strategies and reasons for patient refusal have been limited.

The analysis presented at the 2025 symposium represents the first multicenter evaluation of patients enrolled in PREFER between November 2012 and December 2024. PREFER was conducted at 23 Italian centers. Inclusion criteria included stage I to III invasive breast cancer, premenopausal status at diagnosis, age 18 to 45, and candidacy for neoadjuvant or adjuvant chemotherapy. Patients with stage IV disease, prior chemotherapy or radiotherapy, severe psychiatric disorders, or inability to provide consent were excluded.

The primary objective was to evaluate patient needs and choices regarding ovarian function and fertility preservation, including acceptance rates and reasons for refusal. Secondary objectives included safety of controlled ovarian stimulation for oocyte cryopreservation in patients 40 years or younger, with disease-free survival and overall survival as endpoints. Subgroup analyses were performed according to hormone receptor status.

Key Findings: Fertility Preservation by Age and Hormone Receptor Status

In patients aged 41 to 45 years, 78% of those with hormone receptor-positive disease chose GnRHa alone, while 22% had no procedure. Among hormone receptor-negative patients, 69% received GnRHa alone and 31% declined any intervention. The most frequently reported reason for refusal in this age group was completion of family planning (11%).

Among patients 40 years or younger with hormone receptor-positive disease, 90% received GnRHa, 26% underwent cryopreservation, and 8% had no procedure. For hormone receptor-negative patients, 87% received GnRHa, 21% underwent cryopreservation, and 12% had no procedure. Younger age strongly predicted oocyte cryopreservation, as did having no prior children, more recent year of diagnosis, and lower tumor grade. Hormone receptor-negative status was associated with lower uptake relative to hormone receptor-positive disease.

Patients who underwent oocyte cryopreservation (127 patients) were younger, with a median age of 33, compared with 36 among those who did not pursue cryopreservation (406 patients). Parental status strongly influenced decisions: 87% of patients who pursued cryopreservation had no prior children compared with 35% who did not. Tumor grade and type of chemotherapy also differed between groups, with anthracycline- and taxane-based regimens more frequently used in patients not undergoing cryopreservation.

Safety and Clinical Implications

Among patients 40 years or younger, disease-free survival remained high in both groups. Four-year disease-free survival was 95% in patients who underwent oocyte cryopreservation versus 87% among those who did not. Overall survival at four years was 97% in those who had cryopreservation versus 96% in those who did not. These results suggest that undergoing controlled ovarian stimulation does not negatively affect outcomes.

“Results from the PREFER study may provide novel prospective evidence to improve oncofertility counseling for premenopausal women with early breast cancer. From a public health perspective, these findings may help optimize collaboration between oncology and fertility units, including resource allocation,” Lambertini concluded.

Reference

1. “Fertility and ovarian function preservation in premenopausal women with early breast cancer: results from the multicenter prospective PREgnancy and FERtility (PREFER) study,” by Matteo Lambertini. Presented at: San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract GS3-02.

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