Fertility Preservation and Assisted Reproduction in Patients With Breast Cancer

Concerns About Interrupting Treatment

Fertility during and after treatment is a major concern for young women diagnosed with breast cancer. In hormone receptor-positive early breast cancer, adjuvant endocrine treatment lasts 5 to 10 years, potentially a critical period for fertility. A central concern is whether temporarily interrupting endocrine therapy or using assisted reproductive techniques increases recurrence risk.

The POSITIVE Study

POSITIVE was designed to address these concerns and assess the safety and effectiveness of pregnancy attempts. It was detailed in an article published on May 29, 2024, in JCO entitled "Fertility Preservation and Assisted Reproduction in Patients With Breast Cancer Interrupting Adjuvant Endocrine Therapy to Attempt Pregnancy".

POSITIVE Findings

1. Effects of Interrupting Endocrine Therapy

The primary analysis examined how temporary interruption of adjuvant endocrine therapy affected breast cancer outcomes.

• At a median follow-up of 41 months, the risk of recurrence was not increased in the study.
• Temporary interruption may therefore be a safe option when appropriately managed.

2. Safety of Assisted Reproduction

• Patients using assisted reproduction were compared with those conceiving spontaneously:
• No adverse effect on recurrence was observed with assisted reproduction.
• This supports its safe use in patients with breast cancer.

3. Pregnancy Success by Age

• Women Under 35: 80% achieved at least one successful pregnancy.
• Women Aged 40-42: 50% achieved pregnancy.
• Assisted reproduction played an important role in reducing age-related differences.

Factors Influencing Pregnancy Success

Age

• Age is a major determinant. Attempting pregnancy at a younger age improves success.

Chemotherapy

• Gonadotoxic chemotherapy, including cyclophosphamide- and anthracycline-containing regimens, carries greater infertility risk.
• Ovarian suppression with GnRH analogs may reduce these risks.

Assisted Reproduction

• Assisted techniques increase pregnancy rates, particularly after chemotherapy and in women who have not previously given birth.
• Alternative strategies may be considered when time or socioeconomic barriers limit access.

The Role of GnRH Analogs

GnRH Analogs and Fertility Preservation

These are synthetic derivatives of hypothalamic gonadotropin-releasing hormone (GnRH) used in treatment. Agonists and antagonists are the two groups.

They may be needed when: 

• Hormone receptor-positive breast cancer requires estrogen suppression before menopause;
• Fertility preservation is planned before chemotherapy;
• High-risk patients are considered suitable for ovarian suppression.

Treatment may generally be given during or after chemotherapy for 2-5 years under specific protocols. Duration depends on general condition, tumor stage, and monitoring of postmenopausal hormone levels.

Use during chemotherapy may reduce ovarian failure:

• Meta-analyses suggest that GnRH analogs may increase pregnancy rates.
• They may offer an alternative when assisted reproduction is inaccessible.

Returning to Endocrine Therapy and Adherence

Return to Treatment

In POSITIVE, 74% resumed endocrine therapy after attempting pregnancy, higher than in the general breast cancer population.

• Adherence Strategies: A pregnancy-related break improved treatment adherence in some patients.

Long-Term Follow-Up

Recurrence risk in hormone-sensitive breast cancer can persist for years:

• The study plans 10 years of follow-up.
• Long-term data will clarify later pregnancy outcomes and cancer recurrence.

Pregnancy Planning in High-Risk Patients

Advice for Stage 3 Disease

Recommendations are more complex for women with stage 3 HR-positive breast cancer:

• High Recurrence Risk: Although pregnancy does not increase recurrence risk, detailed assessment is needed.
• An Individualized Approach: Consider age, general health, and pregnancy wishes in a personalized plan.

CDK4/6 Inhibitors and Fertility

The fertility effects of adjuvant CDK4/6 inhibitors, such as abemaciclib and ribociclib, remain under investigation.

• Some studies suggest minimal effects on ovarian function.
• GnRH-based ovarian protection may be considered for these patients.

General Advice and Future Research

Individual Counseling

• Discuss pregnancy plans early.
• Offer detailed fertility-preservation options to younger patients and those without previous births.

Commentary

Further POSITIVE analyses will focus on breastfeeding, ovarian reserve, and long-term fertility. More research is needed on the effects of different regimens.

In conclusion, POSITIVE found pregnancy attempts safe in HR-positive breast cancer and suggested that assisted reproduction can improve success. Appropriately managed temporary endocrine interruption did not increase recurrence risk. Future studies will clarify long-term outcomes and fertility effects of newer treatments.