What does this research mean for the field?

Oncofertility counseling and fertility preservation must be integrated into breast cancer treatment planning, with precautionary approaches applied to newer targeted therapies due to a lack of prospective human fertility data. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The aim is to explore the implications of modern breast cancer therapies on fertility preservation and patient counseling.

May 31, 2026Open Access

Oncofertility in the Age of HER2 Blockade, Immunotherapy, PARP inhibitors, CDK4/6 inhibitors and Endocrine Treatment: Unanswered Questions in Breast Cancer

Key Points

The aim is to explore the implications of modern breast cancer therapies on fertility preservation and patient counseling.
Focus on the impact of various therapies including HER2-blockade and PARP inhibitors on fertility.
Emphasis on integration of fertility considerations into treatment planning from diagnosis and referral for preservation.
Advocacy for the development of reproductive endpoints in clinical trials.
Fertility considerations can affect treatment decisions and should be discussed at diagnosis.
Ovarian suppression during chemotherapy is recommended for eligible patients to mitigate gonadotoxic risks.
Pregnancy during HER2 treatment is not advised due to safety concerns.

Abstract

Opinion Statement As survival among reproductive-age patients with breast cancer continues to improve with modern therapies, concerns regarding fertility preservation, gonadotoxicity, and pregnancy safety have become increasingly prominent. Fertility considerations are well-recognized contributors to treatment refusal and premature discontinuation, therefore, oncofertility counselling should be initiated at diagnosis and integrated into therapeutic planning. Prompt referral for fertility preservation is essential for patients who may wish to conceive, without compromising oncologic outcomes. Systemic therapy selection should remain driven by tumour biology and recurrence risk; however, when clinically equivalent regimens are available, those with lower gonadotoxic potential are preferred. Cytotoxic chemotherapy is the main determinant of permanent ovarian insufficiency, and temporary ovarian suppression during chemotherapy should be routinely considered in appropriate candidates. Endocrine therapy is not associated with irreversible ovarian damage, but its long duration necessitates individualized planning for pregnancy, including supervised treatment interruption in selected low-risk patients. HER2-monoclonal antibodies should be delivered according to standard indications, as it does not appear to confer substantial additional ovarian toxicity beyond chemotherapy; however, pregnancy must be avoided during treatment. For antibody–drug conjugates, PARP inhibitors, and CDK 4 and 6 inhibitors, the absence of prospective human fertility data supports a precautionary approach, including pre-treatment fertility preservation, effective contraception during therapy, and adherence to recommended washout periods. Given the substantial gaps in clinical evidence, transparent communication of uncertainty is essential. The integration of standardized reproductive endpoints into clinical trials, alongside the development of predictive tools is critical to support evidence-based counselling and optimize long-term survivorship outcomes.

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