Selected Advances in Young Women’s Breast Cancer Research and Treatment: Highlights from Recent Scientific Conferences

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The incidence of breast cancer in women is increasing, especially among those under 40, including the rate of metastatic breast cancer, which has grown by 3.5% annually from 2004 to 2017.[1,2] Younger women are diagnosed more often with aggressive subtypes of the disease and are more likely to experience recurrence within 5–10 years after treatment. GENETIC PREDISPOSITION AND RISK FACTORS Genetic predisposition, especially BRCA mutations and a family history of breast cancer, is also common in women under 40. A thorough genomic analysis of patients with metastatic breast cancer in the STING study, using liquid biopsies, found age-related differences in tumor biology. Among young adults (≤40 years), RB1 and PIK3CA mutations were less common in luminal metastatic breast cancer, whereas PTEN mutations were more frequently seen in triple-negative disease cases.[3] Oncology conferences have increasingly highlighted breast cancer in young women, particularly on factors associated with increased risk and disease onset. At the 2024 San Antonio Breast Cancer Symposium (SABCS), key risk factors were highlighted, including a family history of cancer, early alcohol use, and a body mass index ≥25 kg/m2.[4] Conversely, pregnancy appears to have a protective effect, attributed to changes in both the proliferative behavior of mammary epithelial cells and the structural organization of breast tissue. These changes include modifications in collagen composition and alignment, as shown by microscopic techniques such as collagen staining, as well as epigenetic modifications induced during pregnancy.[5] The role of systemic inflammation has also been studied, especially in cases of infections like urinary tract infections. These infections have been shown to trigger systemic inflammatory responses, which may lead to increased collagen buildup in breast tissue, potentially affecting the tumor microenvironment.[6] Results of a large international study presented by Matteo Lambertini et al. showed that among 5290 young women (≤40 years old) diagnosed with breast cancer who were carriers of germline BRCA mutations, those who underwent a bilateral risk-reducing mastectomy (RRM) and/or a risk-reducing salpingo-oophorectomy (RRSO) had significantly better outcomes.[7] Specifically, RRM and/or RRSO were associated with a 35% reduction in the risk of death (adjusted hazard ratio [aHR] 0.65; 95% confidence interval [CI] 0.53–0.78; P < 0.001) and a 42% reduction in the risk of recurrence or development of a second primary malignancy (aHR 0.58; 95% CI 0.52–0.65; P < 0.001). The reduction was even more pronounced in breast cancer-free interval (BCFI; aHR 0.55; 95% CI 0.48–0.62; P < 0.001). Among patients who underwent RRSO alone, the risk of death was reduced by 42% (aHR 0.58; 95% CI 0.48–0.71; P < 0.001), and the risk of recurrence or second primary malignancy decreased by 32%–35% (disease-free survival [DFS]: aHR 0.68; 95% CI 0.61–0.77; P < 0.001; BCFI: aHR 0.65; 95% CI 0.57–0.74; P < 0.001). CHALLENGES RELATED TO ENDOCRINE THERAPY Another significant study highlighted the side effects of endocrine therapy in young women. A subgroup analysis from a Brazilian prospective cohort assessed the impact of ovarian function suppression (OFS) on quality of life (QoL) in young women with early breast cancer.[8] In the study cohort, 290 participants received endocrine therapy alone, while 73 received endocrine therapy combined with OFS. Although OFS has been shown to improve survival outcomes in premenopausal women, the study found that those receiving combined therapy reported significantly more sexual dysfunction and a higher incidence of hot flashes, both of which negatively affected overall QoL. These findings highlight the importance of integrating supportive care strategies, including sexual health assessments, into the management of young breast cancer patients undergoing endocrine therapy to mitigate adverse effects and improve survivorship outcomes. At the 2025 St. Gallen International Breast Cancer Conference, special focus was placed on gaps in genomic testing for young women with breast cancer. Iosifidou et al. from Greece highlighted the underuse of genomic risk assessment with Oncotype DX in young women (≤40 years) diagnosed with early-stage ER-positive, HER2-negative, node-negative (ER+/HER2−/N0) breast cancer.[9] In this retrospective cohort of 324 patients (median age 38 years), the median recurrence score was 17. Among them, 41% had a low recurrence score, and 44% had an intermediate score. These findings suggest that a significant proportion of young women with early-stage ER+/HER2− breast cancer could potentially avoid unnecessary chemotherapy and be safely managed with endocrine therapy alone. In addition, the conference featured a dedicated session focusing on the specific needs of young women with breast cancer. Topics covered included breast cancer during pregnancy, fertility preservation after treatment, sexual health in breast cancer survivors, and the long-term toxicities linked to breast cancer therapies. Another key discussion point is the advantage of extending adjuvant endocrine therapy in younger women. At the 2025 ASCO Annual Meeting, a combined analysis of the SOFT and TEXT trials showed that exemestane plus OFS significantly improved DFS, BCFI, and distant recurrence-free interval compared to tamoxifen plus OFS at 15 years.[6] Specifically, 15-year DFS was 74.9% with exemestane + OFS compared to 71.3% with tamoxifen + OFS (HR 0.82; 95% CI 0.73–0.92). This indicates a 3% absolute increase in DFS at 15 years with exemestane + OFS. However, overall survival at 15 years was not significantly different between the two groups (87.8% vs. 87.0%; HR 0.94; 95% CI, 0.80–1.11). These results underscore the importance of considering extended endocrine therapy in high-risk and very young patients, as the risk of relapse remains for several years. Nonetheless, maintaining adherence to long-term endocrine therapy remains a major challenge in this population. CONCERNS AND QUESTIONS ABOUT SURVIVORSHIP The ESMO Breast Cancer Annual Congress 2025 highlighted that the unique challenges related to treatment outcomes and survivorship in young breast cancer patients are an important concern today. Key issues include fertility preservation, family planning, early menopause, sexual dysfunction, body image issues, and disruptions to family and work life. In addition, younger patients are also more vulnerable to psychosocial distress. This context reveals that a 26-item electronic questionnaire given to physicians in December 2023 to evaluate their knowledge, clinical practices, and attitudes about fertility preservation and pregnancy-related issues in patients with advanced breast cancer showed significant gaps: Only 23.3% of respondents said they always feel comfortable discussing these topics with young patients with advanced breast cancer disease.[10] Another important study, the POSITIVE trial, evaluated the safety and feasibility of interrupting adjuvant endocrine therapy to attempt pregnancy in hormone receptor-positive breast cancer patients.[11] The results indicate that temporarily stopping endocrine therapy to pursue conception is safe, with no obvious negative effect on short-term oncologic outcomes. However, concerns about fertility still exist. Biomarkers like low anti-Müllerian hormone <0.5 ng/mL at 3 months after stopping endocrine therapy were linked to reduced ovarian reserve. Overall, 47.7% of participants had decreased ovarian reserve after ceasing endocrine therapy, and 10% met criteria for premature ovarian insufficiency (defined as follicle-stimulating hormone >25 IU/L). These findings highlight the need for personalized fertility counseling and careful reproductive monitoring in young women considering pregnancy after breast cancer. NATALEE AND MONARCHE PIVOTAL TRIALS Finally, the two major oncology congresses recently shared results from subgroup analyses of t

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