Path-for-young
The Personalized Adjuvant Treatment for HR+/HER2- breast cancer for young patients (Path-for-young) project aims to establish and implement a new standard of care for young women with hormone receptor (HR) positive, human epidermal growth factor receptor (HER)2 negative breast cancer.
Rationale
Cancer is one of the leading causes of illness and death worldwide. Among women, breast cancer (BC) is the most common type, with over 2.3 million new cases diagnosed in 2020—a number expected to rise to 3 million by 2040. Around 70-80% of these cases are a specific subtype called HR+HER2- BC, which also accounts for most of the 700,000 annual deaths from breast cancer.
Rethinking Chemotherapy indication
for High-Risk premenopausal Women
Advancements in treatment, including a combination of local and systemic therapies, have significantly improved survival rates. In high-income countries, more than 80% of women diagnosed with early-stage breast cancer (stages I-III) now survive at least 10 years after diagnosis. Over 50 years of clinical trials have confirmed that adjuvant endocrine therapy and chemotherapy can improve overall survival.
The number of younger women being diagnosed with breast cancer (BC) is increasing. In the European Union, about 25% of new cases occur in premenopausal women, while in low- and middle-income countries, this figure can be as high as 55%. Many of these younger patients have high-risk BC, meaning they are often recommended to receive both chemotherapy and endocrine therapy, including ovarian function suppression. However, younger women tend to experience more severe side effects from treatment compared to older patients. These effects include early menopause, infertility, hot flashes, pain, fatigue, sleep problems, sexual health issues, and increased risks of heart disease, bone loss, cognitive decline, and even secondary cancers. Such challenges impact not only patients' quality of life but also their ability to work and their overall well-being, adding stress to caregivers and the healthcare system.
Currently, genomic tests (like Prosigna, Oncotype Dx, and MammaPrint) help determine whether postmenopausal women may benefit from chemotherapy in addition to endocrine therapy. However, there is insufficient evidence to determine whether some high-risk premenopausal women could safely forgo chemotherapy. Premenopausal women with high-risk BC are recommended chemotherapy, since recent trials such as RxPONDER and MINDACT failed to identify a group that could avoid it. Nevertheless, these trials did not include what is now considered the optimal endocrine therapy approach, which combines oral endocrine therapy with ovarian suppression.
A key question remains:
Can we identify a group of premenopausal women with high-risk BC who can safely avoid chemotherapy while being treated with optimal endocrine therapy?
Researchers believe that genomic tests could help answer this question.
In the UK, the OPTIMA trial is already studying whether genomic testing can safely reduce the need for chemotherapy in patients with higher-risk BC. However, this study does not include enough premenopausal women to provide a clear answer. To address this gap, the Path-for-young consortium will launch the Optima-young trial, which will complement the premenopausal patient population recruited in OPTIMA, reaching a target 5,000 premenopausal women overall. Optima-young will be the first study to determine whether some premenopausal patients with high-risk breast cancer can safely skip chemotherapy by using the optimal endocrine therapy guided by genetic testing.
